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    What Is Spermidine? Benefits, Dosage, and Risks

    What Is Spermidine? Benefits, Dosage, and Risks
    September 30, 2023 Vitality Pro

    What Is Spermidine? Benefits, Dosage, and Risks

    Spermidine is a compound known as a polyamine. Found most abundantly in grapefruit, vegetables, and soybean products, research shows that spermidine may offer a host of benefits for human health and longevity. These benefits range from delaying the process of ageing to extending life span and health span. Spermidine also reduces the risk of cognitive decline, promotes autophagy, and protects against the development of cardiovascular disease.

    In this article, we will explore the clinical data behind spermidine supplements, share information on optimal dosages, side effects and risks, and explore the potential health benefits of taking spermidine in supplemental form. 

    Disclaimer: Please note that this guide should never replace the advice of a qualified medical practitioner.

    What is Spermidine?

    In 1678, Dutch scientist Anton Van Leeuwenhoek discovered the compound in human sperm cells. It naturally occurs as part of our genetic makeup, cells, and tissues, essential in regulating cellular function and replication. Spermidine is produced from putrescine, another polyamine.

    Polyamines such as spermidine can bind to a wide range of different molecules, allowing them to support a range of physical processes, including:

    • DNA replication and repair
    • Cell growth and division
    • Apoptosis (the programmed death of cells)

    Research shows that polyamines function in a way similar to growth factors in the process of cell division, making them essential for healthy cell function and tissue growth and repair.

    Moreover, clinical data shows that spermidine can actually grant human white blood cells anti-inflammatory properties by promoting mitochondrial AMPK activation and autophagy, a process of ensuring that cellular waste is effectively broken down and removed and that cell components, including mitochondria, are recycled. While further research is needed, researchers believe that polyamines can play a vital role in the management of inflammatory conditions and diseases.

    How Does Spermidine Work and Potential Health Benefits

    Spermidine offers a variety of notable health benefits. Numerous research papers state that it offers neuroprotective, cardioprotective, and mitochondrial health-boosting properties when taken as a supplement.


    Spermidine is a chemical in our bodies that has several important roles. It helps regulate the pH levels inside cells and keeps cell membranes stable. This means it helps cells maintain their proper balance and structure. Research has shown that spermidine is involved in brain functions too. It affects receptors related to aspartate (a type of amino acid), activates certain cellular pathways (like cGMP/PKG), helps in the production of nitric oxide, and enhances activity in parts of the brain responsible for processing information.

    One of the most interesting roles of spermidine is its ability to trigger autophagy. Autophagy is like a cleaning process inside cells where they get rid of damaged or unnecessary parts, serving as what is know as a morphogenetic determinant. Triggering spermidine autophagy is the primary mechanism by which spermidine slows the process of ageing and improves longevity. This is shown in a number of animal studies on mice, flies, worms, and yeast cells.

    While these effects are promising, there’s still more to learn about how spermidine works in humans. However, it’s known that when there’s not enough spermidine or when the autophagy process doesn’t work properly, it can lead to increased stress, inflammation, and potentially a shorter lifespan. This suggests that maintaining proper levels of spermidine and ensuring effective autophagy are important for overall health and longevity.


    Some research suggests that Spermidine also has potent anti-inflammatory properties and plays roles in cell growth and division, cell apoptosis, and lipid metabolism. 

    Inflammation is a natural process that accelerates the regeneration of damaged tissues. But when it becomes chronic, it can drive the development of a wide range of age-related diseases, from cardiovascular disease and cognitive decline to type II diabetes, dementia, Alzheimer’s disease, and more.

    Spermidine supplementation appears to limit chronic inflammation, thereby lowering the risk of developing these conditions. It looks to do this by reducing the production of pro-inflammatory molecules by the body. It specifically reduces the creation of substances, known as cytokines, that cause inflammation by decreasing the activity of the genes that make these substances. Cytokines are signalling proteins that are key in triggering and sustaining inflammatory responses. By controlling their production, spermidine helps in reducing inflammation​.


    Another known regulator of human lifespan is how efficiently fat is metabolised. This is regulated by spermidine via adipogenesis, the production of fat cells.

    It is important to understand not all fat cells are inherently bad; they serve several important functions in the body. They are crucial for storing energy, which is used during times when food intake is low or energy demand is high. Fat cells also provide insulation, helping to maintain body temperature and act as a protective layer for organs and tissues. Additionally, they produce vital hormones, such as leptin and adiponectin, which regulate appetite, and metabolism, and have anti-inflammatory effects. Properly functioning fat cells are key to metabolic health, as they prevent the harmful accumulation of fat in organs like the liver and muscles. 

    Mature fat cells are those responsible for most of the beneficial outcomes above. Spermidine may be able to positively modify fat levels in the body by supporting the transformation of preadipocytes (early-stage fat cells) into mature fat cells

    One study noted that patients who received DFMO (difluoromethylornithine), a compound which decreases polyamine production, experienced complete halts in their adipogenesis. This disruption was successfully reversed with a spermidine supplement despite the DFMO still present in the test subjects’ bloodstreams. Researchers think spermidine helps develop fat cells by restoring the activity of specific proteins needed for early-stage fat cells to mature into fully developed fat cells.

    Cognitive Function

    Recent data published in the journal Cell Reports notes that dietary spermidine intake effectively improves mitochondrial function and cognition in both mouse and fly models. It suggests that dietary spermidine can pass the blood-brain barrier in mice and up-regulate a specific biochemical process in a region of the brain associated with memory and learning, known as the hippocampal eIF5A hypusination, and mitochondrial function to enhance brain function. 

    Researchers noted that spermidine supplementation in aged mice improved spatial learning, performance in home-cage environment tasks, and the efficiency of how brain cells use oxygen to produce cellular energy. Additionally, the study proposes higher dietary intake of spermidine may reduce the risk of cognitive impairment and decline. It should be noted that this research is still in its elemental phases and does pose some limitations. More data is needed to fully understand how spermidine and polyamine supplementation can benefit human cognitive function. 

    Other research on human patients yields promising results, too. One study from 2021 notes that spermidine can facilitate the dissolving of amyloid-beta plaques, responsible for neurodegenerative diseases, via the process of autophagy, leading to improvements in the symptoms experienced by senior adults with dementia. The researchers conducted memory tests on older adults taking oral spermidine supplements and took blood samples to determine spermidine concentration and metabolic parameter measurements. 

    The study’s results show a potential link between spermidine intake and improvements in cognitive performance in seniors with mild to moderate dementia. The control group with lower spermidine intake and blood levels showed no improvements or declines in their own cognitive function.

    Lower Cancer

    Some studies have looked into spermidine as a potential substance that might help against cancer, but the results are not definitive. One 2018 research paper suggests that eating more foods containing spermidine might be linked to a lower risk of dying from cancer, but this association is not fully established. Additionally, spermidine might play a role in controlling cancer growth by affecting polyamine metabolism and the body’s immune response to cancer, but this is still a theory. The latter study suggests spermidine could be a rational target for clinical cancer therapies and chemoprevention.

    Moreover, some laboratory research notes that spermidine and similar compounds have shown some ability to initiate cell death processes in various cancer cells, including those in the liver, skin, colon, prostate, and breast. These compounds also seem to affect certain leukaemia and breast cancer cell lines. However, these findings are preliminary and require further investigation before any clear conclusions about their effectiveness in cancer treatment can be drawn.

    Cardiovascular Health

    Research published in the journal Nature Medicine notes that dietary intake of spermidine can effectively extend life span while reversing age-related cardiac dysfunction in mouse models. The spermidine supplements were found to protect cardiovascular health through the induction of cardiovascular autophagy. 

    Mice fed spermidine showed notable improvements in key metrics of heart ageing, including diastolic dysfunction and increased left ventricular stiffness and hypertrophy. These improvements were independent of the impact on insulin function, body composition, lipid profiles, and blood pressure.

    While further research is needed, researchers and other epidemiological studies theorise that spermidine offers similar protective abilities for human cardiovascular health. The researchers report links between survey-reported intake of foods rich in spermidine and reduced rates of cardiovascular disease development in humans.

    Spermidine for Hair Growth

    Research suggests that spermidine hair growth supplements may effectively stimulate human hair growth and modulate the biology of epithelial stem cells. While further research is needed on the effects of spermidine on hair growth, preliminary data shows that the compound promotes hair shaft elongation and prolongs the hair growth period, also known as anagen. 

    The researchers found that spermidine upregulated the expression of epithelial stem cell-associated keratins K19 and K15. It also upregulated certain target genes involved in cell migration and adherence and mitochondrial functions SLC25A3, SYVN1, and NACA. Ultimately, the research suggests that spermidine could be an effective hair growth stimulant, and researchers note that polyamines such as spermidine could be important modulators of normal hair growth patterns.

    Longevity and Lifespan

    Various animal studies have suggested that spermidine supplements can increase the life spans of test subjects while preventing the development of diseases like hepatocellular carcinoma and liver fibrosis. A polyamine-rich diet may exert similar effects, and some data notes that this can improve resilience to stress and age-related disease onset.

    Sources and Forms

    Spermidine is a naturally occurring substance that can be found in a variety of foods commonly included in standard modern diets. It is also available in supplement form in a number of different options, as we will explore below.

    Spermidine Rich Foods

    There are many foods high in spermidine that can help to supplement your levels of this essential polyamine. Some of the best spermidine foods to add to your diet include wheat germ, soya beans, dairy products (cheddar cheese is a particularly good source), rice bran, mushrooms, and chicken livers.

    Some vegetables, including green peas, cauliflower, corn, and broccoli, contain notable amounts of spermidine, as do natto, green tea, lentils, chickpeas, and mangos. Hazelnuts, grapefruits, and legumes contain moderate amounts of the polyamine, and offer additional health benefits when eaten as part of a balanced diet.

    Spermidine Supplements

    Aside from the spermidine-rich foods mentioned above, another way to boost your spermidine levels is to take a spermidine supplement. These supplements can come in a range of different forms, including capsules, tablets, and powders. You may find spermidine supplements containing either natural spermidine, spermidine hydrochloride, or spermidine trihydrochloride. 

    The natural spermidine supplements are often extracted from wheat germ and contain other polyamines that help to support and sustain healthy spermidine levels in the body. The most effective spermidine supplements are ultimately those which have been third-party laboratory tested for purity, efficacy, and dose standardisation.

    Usage and Recommended Dosage

    The ideal recommended spermidine dosage varies from source to source. Research suggests that a daily dose of 6mg or higher is sufficient to provide significant health benefits.

    Other studies recommend different dosages to address specific conditions and risk factors. For instance, one study conducted on senior adults found that a daily dose of 0.9mg of spermidine alongside other polyamines improved cognitive performance and some biomarkers associated with dementia in the patients.

    Another trial found that the average daily spermidine intake of adults in developed countries is around 10mg. The trial linked this intake with reductions in waist circumference, BMI, and reduced fasting blood glucose levels. This suggests that sufficient spermidine intake may be able to improve metabolic function and reduce the risk of type II diabetes and metabolic disorders.

    Potential Side Effects and Interactions

    Spermidine is generally considered to be safe. It presents a low risk of spermidine side effects when taken as directed by the manufacturer. Allergic reactions to spermidine supplements are rare but can occur. If you experience side effects such as persistent nausea, diarrhoea, and vomiting, approach a qualified medical professional as soon as possible for advice.

    Spermidine toxicity is another rare condition that may occur in patients taking high doses of the supplement for extended periods of time. You can reduce your risk of experiencing spermidine side effects and supplement toxicity and tolerance build-up by staying at or below a dose of 3mg per day unless advised to take a higher dose by a medical practitioner. 

    If you are pregnant, breastfeeding, or thinking of giving supplements to a child, seek out the advice of your doctor beforehand to find the best dosage for your needs. There is limited safety data on the use of spermidine during pregnancy and breastfeeding. This supplement should not be given to children unless it is advised by a licensed doctor.

    The best way to supplement safely and effectively with spermidine is to choose a high-quality, third-party-tested supplement produced by a trusted supplier like Vitality Pro. Many clinical studies also use and recommend spermidine in combination with other polyamines to enhance the effects of spermidine supplementation and maintain consistent levels of the compound in the body.


    Spermidine offers a wide range of science-backed benefits for human health, wellness, and longevity. It can reduce the risk of cancer and heart disease, improve cognitive function, lower chronic inflammation, and induce autophagy. Additionally, it lowers the risk of many age-related diseases and disorders, including dementia, Alzheimer’s disease, type II diabetes, and cardiovascular dysfunction.

    If you are interested in any of spermidine’s benefits, it’s important to select a quality, standardised spermidine supplement such as Vitality Pro’s Spermidine, which also contains zinc and thiamine to optimise spermidine levels and bio-availability at a cellular level. 

    Remember to discuss any new supplements you take with your healthcare advisor to ensure that you take the right supplements and dosages to meet your needs.

    Frequently Asked Questions

    What is spermidine used for?

    Studies show that spermidine can induce the process of autophagy to offer a range of anti-inflammatory, anti-cancer, and anti-ageing effects. It also has positive effects on heart health and cognitive function and may help to increase both life span and health span in humans.

    Which foods contain the most spermidine?

    Wheat germ is the richest natural source of spermidine, and the compound can also be found in natto, cheese, soya beans, rice bran, mushrooms, grapefruits, and green peas.

    Can I use spermidine if I am pregnant or breastfeeding?

    Speak to your doctor before starting any new supplement regime if you are pregnant and breastfeeding. While some pregnant or breastfeeding women can take spermidine safely, your medical professional can provide advice on the best dosages and options for your needs.

    Which is the best spermidine supplement to use?

    The best spermidine supplements are those tested by third-party labs for purity and efficacy. Some research recommends the use of spermidine in conjunction with other naturally occurring polyamines to maximise its effects and boost spermidine levels in the body.

    Glossary of Terms

    Adipogenesis: the process of cellular differentiation to produce fat cells from stem cells or progenitor cells found in bone marrow.

    Apoptosis: the natural, programmed death of cells.

    Autophagy: a programmed degradation of cells that removes dysfunctional and damaged components through a mechanism dependent on lysosome activity.

    Cerebral cortex synaptosome: isolated synaptic neuron terminals found in the cerebral cortex of the brain.

    Cytoprotective: protective of cells and cellular activity.

    Diastolic dysfunction: a heart condition characterised by stiffened ventricles and reduced blood flow.

    Left ventricular hypertrophy: a condition in which the left ventricle of the heart – the heart’s primary pumping chamber – becomes stiffened and thickened, reducing its function.

    Left ventricular stiffness: an indicator of the onset of left ventricular hypertrophy (see above).

    Polyamine: an organic compound which contains more than two amino groups. Spermidine, spermine, and putrescine are all classified as polyamines.

    Ribosomes: Small particles which consist of RNA and other proteins which work together to synthesise proteins throughout the human body.

    Standardisation: in the context of supplements, standardisation refers to the process of manufacturing products that contain consistent doses of their active ingredients for maximum efficacy.