Does Spermidine Improve Memory & Cognition?

Q: What is spermidine?

Spermidine is a powerful polyamine that promotes autophagy , the body’s cellular “clean-up” process, and inhibits 9 of the 12 scientifically identified root causes of aging, known as the “Hallmarks of Aging.” While two-thirds of the body’s spermidine is produced by the gut and body tissues, the remaining third comes from food. As we age, natural spermidine production declines, so maintaining youthful levels requires external sources, either from spermidine-rich foods or supplements like Primeadine.

Dec 13, 2024

By Georgia Pilling

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Spermidine and Memory and Cognition | Oxford Healthspan

The search for ways to enhance memory and cognitive health has highlighted a fascinating compound called spermidine. A naturally-occurring polyamine that we naturally produce but declines with age, spermidine is gaining attention for its potential to support brain health and memory impairment in older individuals.

What is Spermidine?

Spermidine is part of a family of compounds called polyamines that play a big role in how our cells grow and repair themselves. It was originally discovered in human sperm—hence the name—but today we know it is present in many parts of the body and in certain foods, such as wheat germ, soybean and shiitake mushrooms [1].

One of its most exciting roles is in a process called autophagy, which you can think of as the body’s natural "cleaning system" [2]. Autophagy helps cells get rid of damaged parts, keeping them functioning at their best. This cellular clean-up is particularly important for brain cells, which need to stay in top shape to keep up with the demands of thinking, learning, and remembering.

How Does Spermidine Act on the Brain?

One reason spermidine has sparked so much interest is for its ability to cross the blood-brain barrier, a protective shield that keeps harmful substances out of the brain [3]. Once in the brain, spermidine gets to work:

Supporting the brain’s ability to clear out waste and repair itself, which is essential for long-term health.
Helping to build and maintain connections between brain cells, which are critical for learning and memory.
Improving energy production in brain cells, ensuring they function efficiently.
Reducing inflammation (one of the hallmarks of aging) in brain tissue, protecting against damage over time.

By promoting these processes, spermidine creates an environment where the brain can perform at its best, whether you’re learning something new or recalling important information.

Spermidine and Memory: What Does the Research Say?

The evidence supporting spermidine's role in enhancing memory is becoming increasingly robust. Animal studies have provided some of the most compelling insights, showing how spermidine supplementation can mitigate age-related cognitive decline. For example, older mice given spermidine performed significantly better on memory tests compared to those that didn’t receive the compound [4]. They demonstrated improved abilities in spatial navigation, like completing mazes, and object recognition tasks, such as distinguishing between familiar and new items. These results suggest that spermidine might help reverse some of the typical effects of aging on the brain by enhancing its functional capacity.

In human studies, although still in the early stages, the findings are equally encouraging. One clinical trial observed that individuals who supplemented with spermidine for several months experienced marked improvements in memory performance. They were better able to recall information and process new data more quickly, a critical aspect of cognitive sharpness. Notably, participants also showed improvements in memory consolidation during sleep, a phase when the brain processes and organizes information gathered throughout the day [5]. These results are particularly exciting because they highlight spermidine’s potential to enhance not just everyday memory but also the deeper, more structural aspects of cognitive health.

Beyond Memory: Other Cognitive Benefits of Spermidine

Spermidine's benefits in the brain go beyond memory enhancement, touching on several key aspects of cognitive health.

Focus and Attention

For those struggling to stay focused or juggle multiple tasks, spermidine might offer a natural solution. Emerging studies suggest that the compound helps improve attention span, making it easier to stay engaged in mentally demanding activities [6]. This effect is likely linked to its role in promoting healthy synaptic connections, which facilitate efficient communication between brain cells. Enhanced focus can have far-reaching benefits, from increased productivity to better learning outcomes.

Neuroprotection and Resilience

One of the most promising aspects of spermidine is its potential to protect the brain against age-related decline. Chronic inflammation and oxidative stress are two significant contributors to conditions like Alzheimer’s disease and other forms of dementia. Spermidine’s ability to reduce inflammation in neural tissue and support the brain's natural "cleaning" processes through autophagy makes it a potent neuro-protective agent [7]. These mechanisms help preserve brain cells and maintain their functionality over time, potentially delaying or preventing the onset of cognitive decline.

Enhancing Neuroplasticity

Neuroplasticity—the brain’s capacity to adapt and reorganize itself—is a cornerstone of learning and cognitive resilience. This adaptability allows us to form new neural connections, acquire new skills, and recover from injuries or age-related decline. Spermidine appears to enhance neuroplasticity by encouraging the repair and growth of synaptic connections and by maintaining cellular energy production through healthier mitochondria [8]. This means that spermidine could not only help us retain what we already know but also enable us to keep learning and adapting as we age.

Mood and Emotional Regulation

While not as extensively studied as its effects on memory and focus, preliminary research suggests that spermidine might have a positive impact on mood and emotional stability. By reducing inflammation and oxidative stress and supporting gut health—factors often linked to mood disorders like depression—spermidine may contribute to a healthier emotional state [9].

What’s Next for Spermidine Research?

Scientists are just beginning to scratch the surface of what spermidine can do. Current studies are focused on understanding how it works over the long term, what doses are most effective, and whether combining it with other brain-boosting compounds can amplify its effects. There’s also growing interest in how spermidine might help prevent or slow cognitive decline in conditions like Alzheimer’s disease.

While we wait for more definitive answers, the research so far is promising enough to suggest that spermidine is a key tool in supporting brain health.

What’s Next for You? Incorporating Spermidine into your Daily Routine

Incorporating spermidine into your daily routine doesn’t have to be complicated. This powerful compound is naturally found in many common foods. Wheat germ, a versatile ingredient for smoothies or baked goods, is one of the best sources. Other rich options include aged cheeses like parmesan, mushrooms, soybeans, and fermented foods such as natto or miso.

However, if you’re looking for a more convenient and consistent way to ensure you're getting enough to support your cognitive health, supplementation can be a great option. That’s where Primeadine®, Oxford Healthspan’s premium spermidine supplement, comes in. Primeadine® stands out with its pure, food-derived spermidine from Japan, ensuring a clean, bioavailable supplement without synthetic additives and guaranteed potency, purity, and safety through rigorous third party testing. Backed by cutting-edge science and developed with leading scientists, Primeadine® is crafted to work effectively at the cellular level.

References

[1] Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018). Spermidine in health and disease. Science, 359(6374), eaan2788. DOI: 10.1126/science.aan2788

[2] Eisenberg, T., Knauer, H., Schauer, A., et al. (2009). Induction of autophagy by spermidine promotes longevity. Nature Cell Biology, 11(11), 1305–1314. DOI: 10.1038/ncb1975

[3] Gupta, V. K., Scheunemann, L., Eisenberg, T., et al. (2013). Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner. Nature Neuroscience, 16(10), 1453–1460. DOI: 10.1038/nn.3512

[4] Schroeder S, Hofer SJ, Zimmermann A, Pechlaner R, Dammbrueck C, Pendl T, Marcello GM, Pogatschnigg V, Bergmann M, Müller M, Gschiel V, Ristic S. Dietary spermidine improves cognitive function. Cell Rep. 2021 Apr 13;35(2):108985. doi: 10.1016/j.celrep.2021.108985

[5] Schwarz C, Benson GS, Horn N, Wurdack K, Grittner U, Schilling R, Märschenz S, Köbe T, Hofer SJ, Magnes C, Stekovic S, Eisenberg T, Sigrist SJ, Schmitz D. Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial. JAMA Netw Open. 2022 May 2;5(5):e2213875. doi: 10.1001/jamanetworkopen.2022.13875. PMID: 35616942; PMCID: PMC9136623

[6] Ni YQ, Liu YS. New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases. Aging Dis. 2021 Dec 1;12(8):1948-1963. doi: 10.14336/AD.2021.0603. PMID: 34881079; PMCID: PMC8612618

[7] Wang IF, Tsai KJ, Shen CK. Spermidine on neurodegenerative diseases. Cell Cycle. 2015;14(5):697-8. doi: 10.1080/15384101.2015.1006551. PMID: 25715121; PMCID: PMC4614629

[8] Ferchmin PA, Eterović VA. Role of polyamines in experience-dependent brain plasticity. Pharmacol Biochem Behav. 1987 Feb;26(2):341-9. doi: 10.1016/0091-3057(87)90128-6. PMID: 2437595

[9] Qi G, Wang J, Chen Y, Wei W, Sun C. Association between dietary spermidine intake and depressive symptoms among US adults: National Health and Nutrition Examination Survey (NHANES) 2005-2014. J Affect Disord. 2024 Aug 15;359:125-132. doi: 10.1016/j.jad.2024.05.041. Epub 2024 May 8. PMID: 38729223

Georgia Pilling, BSc, Physiological Sciences (Newcastle University); MRes, Neuroscience (Newcastle University)

Georgia Pilling is a researcher interested in enhancing human longevity through optimizing physiological health and cognitive function. She holds a Bachelor's degree in Physiological Sciences (BSc) and a Master of Research in Neuroscience (MRes) from Newcastle University. Her particular area of intrigue is cognitive neuroscience, passionate about sharing practical strategies for improving brain function and overall mental well-being. In her free time, Georgia enjoys yoga, running, and experimenting with cooking.

FAQs

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What is spermidine?

Spermidine is a powerful polyamine that promotes autophagy, the body’s cellular “clean-up” process, and inhibits 9 of the 12 scientifically identified root causes of aging, known as the “Hallmarks of Aging.” While two-thirds of the body’s spermidine is produced by the gut and body tissues, the remaining third comes from food. As we age, natural spermidine production declines, so maintaining youthful levels requires external sources, either from spermidine-rich foods or supplements like Primeadine.

What are the benefits of spermidine?

Studies link higher levels of spermidine with longevity. Human trials show that food-derived spermidine supports cognition, heart health, hormonal balance, hair growth, collagen production, and nail strength, with potential benefits for fertility and circadian rhythm. These effects stem from spermidine's ability to trigger autophagy—the body's cell renewal process—and inhibit nine of the twelve "Hallmarks of Aging," including inflammation, stem cell and mitochondrial dysfunction, and gut imbalance. Clients also report deeper sleep, increased energy, gray hair reversal, improved skin, and better gut health. Read this blog post to learn more.

What makes Primeadine superior to other spermidine supplements?

While we can’t speak directly about the formulation of other spermidine products, here are some of the main differentiators of Primeadine®/Oxford Healthspan.

We source our raw materials from Japan, which is known for its Nobel Prize-winning scientific leadership on autophagy, or cell renewal. Japan has the most rigorous quality control and testing policies in the world, meaning our ingredients have the most advanced extraction process and meet the incredibly high standards of the Japan Health Food and Nutrition Food Association. They are tested for heavy metals, mold, fungi, and bacteria at the Japan Food Research Lab (JFRL), a third party independent testing lab.
Every single batch is tested for its amount of food-derived spermidine so we ensure it contains the minimum effective dose of 1mg stated on our labels.
Primeadine® is manufactured in Japan in an FDA-registered and -inspected facility with ISO22000 standards, the highest in food quality control. It is then encapsulated in an FDA cGMP facility in the USA and undergoes purity testing there as well at Eurofins or Delta.
Our capsules and tablets do not contain any synthetic ingredients, whereas other supplements typically contain magnesium stearate (of which circa 80% has hydrogenated fats in it; the supplement industry is not legally required to get rid of hydrogenated oils the way the processed food industry has been mandated by law to), shellac, talc and glycerin. Our products are all suitable for vegans. Learn more about our sourcing, quality, and testing standards.
The Primeadine® Original formulation includes a special type of prebiotic fiber, called FOS (fructooligosaccharide), that selectively feeds the friendly, spermidine-producing bacteria in the gut microbiome. The idea is to increase both supplemental, or 'exogenous' spermidine, as well as encourage your own body's natural ability to produce spermidine in your gut microbiome.
Primeadine® GF comes from a sub-strain of chlorella singled out from over 100 others because it alone contains a high level of spermidine and also contains putrescine, the precursor polyamine to both spermine and spermidine. Our chlorella is grown in the nutrient-abundant longevity islands of Okinawa, Japan, and exposed to sunlight to increase the chlorophyll and other nutrient content, such as vitamins D and K, which together help drive calcium to the bones. We combine the chlorella with two other anti-inflammatories and autophagy inducers, Okinawan turmeric and nobiletin (from Okinawan "Shikuwasa" citrus lime peel).
We do not use liposomes in Primeadine® because this is unnecessary for absorption and would prevent the benefits that happen when spermidine is exposed directly to the gut lining. There is no evidence that spermidine cannot be taken up by the cells on its own. Similar to amino acids, polyamines do not need a liposome to cross into the cell or to be taken up with epithelial cells. The process of creating a liposomal version also creates unnecessary expense.
We do not synthetically enrich our product with synthetic spermidine. Be wary of labels that say "wheat germ with spermidine" as this indicates that the wheat germ has been soaked in synthetic spermidine, thereby increasing the overall amount of spermidine but meaning it is no longer a natural source.
We do not use doses beyond what the European Food Safety Authority (EFSA) has mandated as safe for human consumption, which is 6mg daily. Please note that this is related to food-derived spermidine. Synthetic spermidine and synthetically enriched spermidine have never been tested in humans for safety or efficacy and are being sold without regulatory oversight.
We work closely with our scientific and clinical advisers at the University of Oxford and abroad, all of whom take our product and share it with their loved ones. Learn more about our scientific advisory board here.
We are also the only non-Japanese member of the Japan Autophagy Consortium, whose Senior Adviser is the 2016 Nobel Prize Winner in Medicine or Physiology, Prof Yoshimori Ohsumi, and whose Director is Prof Tamotsu Yoshimori, Osaka University. Prof Yoshimori conducted all of the mammalian research in autophagy that helped underpin Prof Ohsumi's work in yeast cells. Find out more about our story here.

What is the best spermidine dose to take?

The US FDA has not set a safe upper limit for food-derived spermidine, but the European Food Safety Authority considers up to 6 mg safe. Most studies use a daily dose of 1 mg of natural spermidine, along with spermine and putrescine, which are absent in synthetic versions. Synthetic spermidine has not been tested for human safety or efficacy.

Why is your spermidine supplement more expensive compared to other products I see on the internet?

We prioritize the highest quality, avoiding common additives like industrial seed oils, magnesium stearate, and talc often used in supplements. Unlike cheap synthetic spermidine often "cut" into products, we use food-derived spermidine sourced and manufactured in Japan under strict regulatory standards. Our products undergo rigorous third-party testing to ensure purity and effectiveness. This commitment to quality, like choosing the best ingredients for a child’s birthday cake, is our guiding philosophy.

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