1) Conditions Studied
Spermidine has been studied for a variety of conditions, including:
- Aging and age-related diseases
- Neurodegenerative diseases such as Alzheimer's and Parkinson's
- Cardiovascular health
- Immune system regulation
- Metabolic disorders
2) Efficacy in Treating Conditions
While research on spermidine is ongoing, some studies suggest that it may have potential in treating or mitigating the effects of the aforementioned conditions. However, more research, especially human clinical trials, is needed to establish its efficacy and safe dosage.
3) Health Benefits
Spermidine has been associated with several health benefits, such as:
- Promoting cellular autophagy, which is the body's way of cleaning out damaged cells, to potentially slow down the aging process
- Possibly improving cardiovascular health by reducing hypertension and enhancing heart function
- Potentially playing a role in cancer prevention and treatment through its effects on cellular processes
- May improve neurological health and protect against neurodegenerative diseases
As with any compound, spermidine may have potential downsides, including:
- Interactions with medications, particularly those affecting polyamine metabolism
- Possible side effects at high concentrations, such as gastrointestinal distress
- Limited information on long-term safety for human consumption
5) Genetic Variations
Research into the relationship between spermidine and genetic variations is in its early stages. Some studies suggest that genetic differences may influence how individuals respond to spermidine, particularly in how it is metabolized and its effects on cell growth and maintenance. It is not yet clear if there are specific genetic variations that would make spermidine particularly beneficial or harmful.
Research Summary on Spermidine
Effects on Heart Health and Longevity
Spermidine (Spd), a polyamine, has been shown to improve heart health and longevity through mechanisms such as autophagy, mitophagy, and improved mitochondrial respiration. It enhances the mechanical properties of cardiomyocytes and is believed to be taken up by these cells, though the entry mechanism is yet to be fully understood.
Role in Intestinal Health
Spermidine is critical for hypusine formation, which is important for protein synthesis and intestinal health. Lower levels of the enzyme required for hypusine production are found in individuals with inflammatory bowel diseases. Hypusination is vital for normal intestinal function, and its deficiency can lead to increased cell proliferation, inflammation, and colon cancer.
Therapeutic Potential in Liver Fibrosis
Low spermidine levels are associated with advanced steatohepatitis. Spermidine supplementation has shown promise in treating liver fibrosis by decreasing extracellular matrix proteins, improving fibrosis, and inhibiting the activation of hepatic stellate cells.
Autophagy and Lifespan Extension
Spermidine and resveratrol can induce autophagy, which is protective and can extend lifespan in various organisms, including yeast, nematodes, flies, and human cells. These effects are linked to modulating acetylation processes within the cell.
Association with Brain Aging
Higher plasma levels of spermidine are associated with markers of brain aging such as reduced hippocampal volume and increased Alzheimer's disease score. Elevated spermidine levels could be early biomarkers for Alzheimer's disease and vascular brain pathology.
Dietary Intake and Health
Higher dietary intake of spermidine could reduce mortality, particularly from cardiovascular diseases and cancer. Spermidine supplementation has been shown to counteract the effects of aging.
Effects on Acute Pancreatitis
Spermidine has therapeutic potential in treating acute pancreatitis by targeting acetylcholinesterase and the serotonin transporter, reducing cell necrosis and inflammation.
Memory Improvement in Aging
Spermidine can counteract memory decline in aging fruit flies by inducing autophagy. It has potential as a treatment for memory loss associated with aging.
Role in Oocyte Quality and Female Reproductive Aging
Spermidine supplementation improves oocyte quality and reproductive outcomes in aged mice by enhancing mitophagy and mitochondrial function.
Prevention of Colitis and Colorectal Cancer
Spermidine supplementation improves colitis and prevents colon cancer by helping regulate colitis, inhibiting tumor development, and modulating the gut microbiome.
Cardiac Aging and Mitochondrial Function
Spermidine supplementation protects against cardiac aging by restoring polyamine levels and activating pathways that promote mitochondrial biogenesis and function.
Impact of Nutrition on Lifespan
Certain nutritional approaches, such as caloric restriction, methionine restriction, lower protein intake, or spermidine supplementation, can extend lifespan. Diets rich in whole grains, vegetables, nuts, and coffee are linked to a lower risk of all-cause mortality.
Protective Effects on Endurance Athletes
A mixture containing spermidine and other natural substances can reduce oxidative stress and muscle injury in athletes, suggesting benefits for muscle recovery.
Supplementation in Hypertension
A mixture including spermidine did not influence blood pressure levels but reduced oxidative stress and stimulated autophagy, potentially beneficial for preventing cardiovascular damage associated with hypertension.
Dementia Diagnostics and Treatments
Oral spermidine supplementation has shown cognitive improvement in older adults with mild to moderate dementia, with high doses associated with increased cognitive performance.
Ovarian Function Protection
Spermidine supplementation can improve ovarian endocrine function and reproductive capacity in mice affected by oxidative stress, suggesting its potential as a novel approach for protecting against ovarian damage.
Protective Effects on the Liver
Spermidine induces a nontraditional pathway involving NRF2, a critical transcription factor for cellular protection, by way of the protein MAP1S, offering liver protection against diseases like fibrosis.
Cardioprotective Agent in Diets
Spermidine serves as a heart-protective agent, enhancing cardiac autophagy and reducing blood pressure. It is associated with a lower risk of cardiovascular diseases.
Immune Function Enhancement
Spermidine supplementation restores autophagy pathway and improves the immune response of aged human B cells, suggesting potential to counteract immune senescence.
Therapeutic Potential for Brain Disorders
Spermidine shows promise in treating brain diseases, extending lifespan, and improving mitochondrial function by promoting autophagy.
Proangiogenic Effects in Aging
Spermidine supplementation has proangiogenic effects, improving the formation of new blood vessels and blood flow in aged mice, with potential treatment for ischemic conditions.
Oxidative Stress Reduction in Aging Mice
Spermidine supplementation reduces oxidative stress in aging mice, extending lifespan and preventing necrotic cell death through autophagy.
Anti-Aging Effects and Autophagy Promotion
Spermidine promotes autophagy, which impacts aging by reducing inflammation, altering lipid metabolism, and influencing cell growth, with the MAPK pathway being a key route for these effects.
Cardiovascular Protection and Heart Function Preservation
Oral spermidine supplementation can extend the lifespan of mice, protect against cardiovascular diseases, reduce heart inflammation, and preserve heart function.
Collagen-Related Muscle Disorders Treatment
Long-term spermidine treatment improves muscle strength, mitochondrial health, and neuromuscular junction integrity in mice with inherited muscle disorders.
Traumatic Brain Injury and Polyamine Catabolism
Changes in polyamine catabolism following traumatic brain injury in rats could lead to a loss of homeostasis in this pathway, suggesting potential treatments involving polyamine supplementation or inhibition of their oxidation.
Impact of Polyamine Intake on DNA Methylation
Increased consumption of polyamines, such as spermine, can reduce age-related DNA methylation errors and extend lifespan in mice, affecting gene methylation enzymes.
Neuroprotective Effects on Mitochondrial Dysfunction
Spermidine improves mitochondrial functions and corrects mitophagy impairments caused by mutant tau protein, indicating potential to counteract tau-related neurodegenerative diseases.
Protection Against Kidney Ischemia and Reperfusion Injury
Spermidine supplementation reduces plasma creatinine levels and tubular injury after kidney ischemia and reperfusion injury, suggesting protective effects against oxidative stress and necrosis.
Memory Performance Improvement in Dementia
Long-term spermidine supplementation shows improvement in memory performance in older adults with dementia, supporting its beneficial impact on cognitive function.
Reduction of Vascular Calcification
Spermidine reduces mineral deposits and calcification in vascular smooth muscle cells and arterial rings, linked to activation of the SIRT1 signaling pathway and reduction in endoplasmic reticulum stress.
Autophagy and Immune Senescence Counteraction
Spermidine modulates autophagy and counteracts immune senescence through the regulation of protein synthesis, with implications for immune system rejuvenation.
Role in Musculoskeletal Diseases
Polyamines like spermidine regulate autophagy naturally and possess anti-aging effects, suggesting potential therapeutic effects in musculoskeletal diseases characterized by muscle atrophy.
Ovarian Aging and Disease
Polyamines support cell growth and development, alleviating ovarian aging and participating in hormone synthesis and cell death regulation. However, excessive levels can contribute to ovarian disease.
Cardiac Mitochondrial Function in Aging
Spermidine supplementation may restore the number of mitochondria and improve their 3D structure in aged hearts, contributing to mitochondrial function and countering aging effects.
Link Between Mitochondrial Function, Brain Aging, and Spermidine
Spermidine promotes mitochondrial respiration and delays brain aging by donating a group required for the hypusination of eIF5A, maintaining mitochondrial health and preventing premature brain aging.
Spermidine and Obesity
Spermidine supplementation shows negative correlation with obesity, leading to weight loss and improved insulin resistance, potentially through enhanced gut health and microbiota function.
Cognitive Function and Dietary Spermidine
Dietary spermidine can improve cognitive function by enhancing hippocampal function and mitochondrial activity, with autophagy playing a key role.
Neuroprotection in Aging Rats
Spermidine supplementation reduces oxidative stress and inflammation, and enhances autophagy in aging rats, indicating potential benefits for age-related neurological conditions.
Combatting Obesity and Metabolic Disorders
Spermidine intake combats obesity and associated metabolic disorders by activating brown adipose tissue and adapting skeletal muscle through both hypothalamus-dependent and independent mechanisms.
Therapeutic Treatment for Genetic Translation-Related Disorders
Spermidine supplementation can partially correct protein translation issues caused by mutations in the EIF5A gene, suggesting its potential as a therapeutic treatment for genetic translation-related disorders.
Universal Anti-Aging Treatment
The external addition of spermidine can extend lifespan and reduce protein damage related to aging in various organisms, indicating its potential as a universal anti-aging treatment.
Autophagy and Longevity
Spermidine induces autophagy in yeast, mammalian cells, nematodes, and flies, which is essential for its life-extending and necrosis-suppressing effects.
Relationship Between Sirtuin-1 and Autophagy
Sirtuin-1 activation, through agents like resveratrol or genetic alterations, initiates autophagy and is necessary for autophagy in response to nutrient deprivation, but not for autophagy activated by downstream signals.
Cardioprotective Effect During Acute Myocardial Infarction
Pretreatment with spermidine reduces cardiac dysfunction during acute myocardial infarction by promoting autophagy and enhancing the heart's antioxidant capacity.
Delaying Aging in Mesenchymal Stromal Cells
Early administration of spermidine significantly delays senescence in human umbilical cord mesenchymal stem cells, maintaining their proliferation and differentiation capabilities.
Liver Endothelium Protection
Dietary spermidine supplementation during early phases of liver disease can protect the liver endothelium from oxidative stress and could alter the progression of chronic liver diseases.
Autophagy Decline and Aging
Spermidine can extend lifespan and improve cellular function by promoting autophagy, which decreases with age and leads to cellular damage accumulation.
Neurological Health and Therapeutic Potential
Spermidine's neuroprotective effects, including anti-aging, anti-inflammatory, and neurotoxicity prevention properties, could be beneficial in treating age-related neurological disorders.
Dietary Polyamines and Health
Dietary polyamines such as putrescine, spermine, and spermidine are critical for cell growth, DNA stabilization, and immune response, and may be supplemented in infant formulas to support neonatal gut development.
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- Beneficial effects of spermidine on cardiovascular health and longevity suggest a cell type-specific import of polyamines by cardiomyocytes
- Hypusination Maintains Intestinal Homeostasis and Prevents Colitis and Carcinogenesis by Enhancing Aldehyde Detoxification
- Spermidine suppresses the activation of hepatic stellate cells to cure liver fibrosis through autophagy activator MAP1S
- Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol
- Association of spermidine plasma levels with brain aging in a population-based study
- Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?
- Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome
- Computational biology-based study of the molecular mechanism of spermidine amelioration of acute pancreatitis
- Polyamines and Aging: A CLEAR Connection?
- Spermidine-triggered autophagy ameliorates memory during aging
- Spermine is a natural suppressor of AR signaling in castration-resistant prostate cancer
- Nutritional Aspects of Spermidine
- Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging
- Protective Role of Spermidine in Colitis and Colon Carcinogenesis
- Spermidine alleviates cardiac aging by improving mitochondrial biogenesis and function
- Nutrition and longevity - From mechanisms to uncertainties
- Natural Activators of Autophagy Reduce Oxidative Stress and Muscle Injury Biomarkers in Endurance Athletes: A Pilot Study
- Effects of two-month treatment with a mixture of natural activators of autophagy on oxidative stress and arterial stiffness in patients with essential hypertension: A pilot study
- The positive effect of spermidine in older adults suffering from dementia : First results of a 3-month trial
- Spermidine suppresses oxidative stress and ferroptosis by Nrf2/HO-1/GPX4 and Akt/FHC/ACSL4 pathway to alleviate ovarian damage
- Advancements in therapeutic drugs targeting of senescence
- Spermidine Confers Liver Protection by Enhancing NRF2 Signaling Through a MAP1S-Mediated Noncanonical Mechanism
- Dietary spermidine for lowering high blood pressure
- Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence
- Spermidine-induced hypusination preserves mitochondrial and cognitive function during aging
- Spermidine improves angiogenic capacity of senescent endothelial cells, and enhances ischemia-induced neovascularization in aged mice
- Induction of autophagy by spermidine promotes longevity
- Molecular basis of the 'anti-aging' effect of spermidine and other natural polyamines - a mini-review
- Cardioprotection and lifespan extension by the natural polyamine spermidine
- Sustained oral spermidine supplementation rescues functional and structural defects in COL6-deficient myopathic mice
- Polyamine catabolism is enhanced after traumatic brain injury
- Extracellular Spermine Activates DNA Methyltransferase 3A and 3B
- Spermidine Promotes Cardioprotective Autophagy
- Spermidine Rescues Bioenergetic and Mitophagy Deficits Induced by Disease-Associated Tau Protein
- Spermidine rescues proximal tubular cells from oxidative stress and necrosis after ischemic acute kidney injury
- The positive effect of spermidine in older adults suffering from dementia after 1 year
- Spermidine inhibits vascular calcification in chronic kidney disease through modulation of SIRT1 signaling pathway
- The curious case of polyamines: spermidine drives reversal of B cell senescence
- Polyamines and Physical Activity in Musculoskeletal Diseases: A Potential Therapeutic Challenge
- Polyamines in Ovarian Aging and Disease
- Spermidine supplementation influences mitochondrial number and morphology in the heart of aged mice
- eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction
- Spermidine improves gut barrier integrity and gut microbiota function in diet-induced obese mice
- Dietary spermidine improves cognitive function
- Spermidine, a caloric restriction mimetic, provides neuroprotection against normal and D-galactose-induced oxidative stress and apoptosis through activation of autophagy in male rats during aging
- Oral Spermidine Targets Brown Fat and Skeletal Muscle to Mitigate Diet-Induced Obesity and Metabolic Disorders
- Spermidine supplementation in rare translation-associated disorders
- Spermidine: a novel autophagy inducer and longevity elixir
- The life span-prolonging effect of sirtuin-1 is mediated by autophagy
- A study of the cardioprotective effect of spermidine: A novel inducer of autophagy
- Spermidine Retarded the Senescence of Multipotent Mesenchymal Stromal Cells In Vitro and In Vivo through SIRT3-Mediated Antioxidation
- Spermidine Supplementation Protects the Liver Endothelium from Liver Damage in Mice
- Polyamines reverse immune senescence via the translational control of autophagy
- Spermidine, an autophagy inducer, as a therapeutic strategy in neurological disorders
- Biological significance of dietary polyamines