The Skin-Deep Benefits of Spermidine: A Comprehensive Look

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.

Oct 16, 2024

By Georgia Pilling

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Mature woman with healthy skin | Oxford Healthspan

Today we're diving into an exciting topic that's been making waves in the skin-care world: spermidine. While it might not be the first thing you think of when considering skincare, this naturally-occurring compound has some impressive benefits that are worth exploring. So, grab yourself a cup of green tea (which, by the way, is rich in spermidine), and let's get into it!

What is Spermidine?

First things first, what exactly is spermidine? Spermidine is a type of polyamine found in all living cells, known to be involved in a number of cellular processes such as growth, proliferation, and regeneration. This molecule is also found in foods like wheat germ, soybeans, aged cheese, and mushrooms.

While spermidine is naturally produced within the body, this production slows as we age and makes us much more reliant on intake from food or supplementation.

Most people know spermidine for its age-defying benefits, with studies showing it to "delay aging" in humans and target the hallmarks of aging, however, it also has the ability to enhance skin health.

The Science Behind Spermidine and Skin Health

Boosting Cellular Renewal

One of the standout benefits of spermidine is its ability to promote autophagy—our body's internal 'housekeeping' process that clears and recycles damaged or dead cells and cell parts.

As cells are foundational to every part of us, this process is crucial for maintaining youthful, vibrant skin. For the skin to perform its protective function, dead skin cells need to be regularly removed. If these cells accumulate, they can irritate the skin and this may trigger an immune response or inflammation [1]. By supporting sufficient autophagy, spermidine helps ensure this process runs smoothly, reducing the risk of skin irritation or unwanted immune reactions [2] (read more on this below).

Improved Skin Barrier Function

The skin barrier is our first line of defence against foreign invaders - like bacteria, toxins, and pollution - therefore, maintaining its integrity is absolutely crucial for healthy skin. Spermidine supports the health of the skin barrier by promoting the growth and differentiation of keratinocytes, the cells that compose the outermost layer of the skin [3]. This helps the skin retain moisture and protects against environmental irritants.

According to research, spermidine helps to enhance skin barrier function, leading to improved hydration and resilience against external stressors [4]. For instance, an animal study published in cell communication and signalling found that both topical and systemically administered spermidine accelerated the skin-wound repair process. This implies that spermidine is supportive in wound healing as well as overall skin health [5].

Anti-Inflammatory Properties

Inflammation is named as one of the hallmarks of aging and can often be a key player in many skin issues. Research has shown that spermidine can effectively modulate the body’s inflammatory response, leading to reduced chronic inflammation—a key factor in skin conditions like acne, eczema, and psoriasis. Spermidine is thought to achieve this through regulating the genetic pathways that control the production of pro-inflammatory cytokines—proteins that are key drivers of inflammation—effectively reducing inflammation at the cellular level [6]. This reduction in inflammation is crucial for managing skin conditions where excessive inflammation can exacerbate symptoms. Additionally, by dampening inflammation, spermidine not only aids in quicker wound healing but also helps to minimise the signs of skin aging.

Antioxidant Effects

Oxidative stress arises when there is an imbalance between free radicals—unstable molecules that can damage cells—and the body's antioxidant defenses. Spermidine, with its powerful antioxidant properties, offers a protective shield against the oxidative stress that accelerates skin aging. While research has demonstrated spermidine's ability to neutralize free radicals in various biological settings [7], its direct impact on skin health hasn't been fully established. However, it’s reasonable to extrapolate that maintaining optimal spermidine levels could help prevent cellular damage caused by oxidative stress. This, in turn, may reduce or delay the formation of wrinkles, fine lines, and the loss of skin elasticity typically associated with aging. By acting as an antioxidant, spermidine could play a key role in preserving youthful, resilient skin.

Collagen Production

Collagen is the protein responsible for keeping our skin firm, plump, and elastic. As we age, collagen production naturally declines, leading to wrinkles and sagging skin. Spermidine has been shown to stimulate collagen synthesis, which can help maintain skin structure and reduce the appearance of fine lines and wrinkles. Research published in Communications Biology in 2021 suggests that spermidine can enhance collagen production, thereby supporting skin's structural integrity and elasticity [8].

The Skin Microbiome

The skin microbiome is composed of millions of beneficial bacteria, viruses, and fungi established at birth and can gradually change with age. Imbalance in this microbiome at any time in the life cycle can contribute to skin diseases and conditions like atopic dermatitis, psoriasis and acnes. In a study conducted in 2021, which explored the age-associated changes of the skin microbiome, spermidine supplementation positively affected the growth of at least two bacteria S. pneumoniae and S infantis that promote positive skin health [8]. Benefits to other players in the skin microbiome remain to be reviewed.

The Gut-Skin Axis

As a final point, it is worth mentioning the gut-skin axis, which refers to the direct communication between the gut and the skin. This connection is regulated through various mechanisms, including the immune system and inflammatory responses. A healthy gut microbiome—a balanced community of microorganisms in the digestive tract—is crucial for maintaining skin health. Disruptions in gut health, known as gut dysbiosis, can negatively affect the skin. According to research, spermidine helps improve gut dysbiosis, stabilizing the gut microbiome. This has a plethora of health benefits (to find out more visit our blog post: Spermidine and the Gut-Brain Connection). A balanced gut microbiome helps regulate systemic inflammation and supports a healthy immune response, which are essential for maintaining clear and resilient skin. Therefore, via this gut-skin axis, spermidine may have an indirect benefit to skin health.

How to Incorporate Spermidine into Your Routine

Now that we know how spermidine benefits the skin, the next question is: how can you incorporate it into your daily routine?

Dietary Sources: Include spermidine-rich foods like wheat germ, soy products, aged cheese, and mushrooms in your diet.

Supplements: Consider spermidine supplements, like Primeadine®, which can provide a more concentrated dose.

Topical Products: Look for skincare products that contain spermidine or promote autophagy for an added boost to your skincare regimen. There are limited quality topical spermidine skincare products on the market, but a top tip (and something many of our clients do) is to add a tsp of our powder or the contents of 3 capsules to a face mask or face cream.

Final Thoughts

Spermidine is proving to be a game-changer in the realm of skin health, offering a range of benefits from boosting collagen production to enhancing the skin barrier and reducing inflammation. While more research is always beneficial, the existing studies paint a promising picture of how this compound can help us maintain healthy, youthful skin.

So, why not give spermidine a try? Whether through diet, supplements, or topical applications, this little molecule might just be the key to unlocking healthy skin as you age!

References:

[1] Sil, P., Wong, S. W., & Martinez, J. (2018). More than skin deep: Autophagy is vital for skin barrier function. Frontiers in Immunology, 9(JUN), 381845. https://doi.org/10.3389/FIMMU.2018.01376/BIBTEX

[2] Hofer, S.J., Simon, A.K., Bergmann, M. et al. Mechanisms of spermidine-induced autophagy and geroprotection. Nat Aging 2, 1112–1129 (2022). https://doi.org/10.1038/s43587-022-00322-9

[3] Yousef H, Alhajj M, Fakoya AO, et al. Anatomy, Skin (Integument), Epidermis. [Updated 2024 Jun 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470464/

[4] Kim, G., Kim, M., Kim, M. et al. Spermidine-induced recovery of human dermal structure and barrier function by skin microbiome. Commun Biol 4, 231 (2021). https://doi.org/10.1038/s42003-020-01619-4

[5] Ito D, Ito H, Ideta T, Kanbe A, Ninomiya S, Shimizu M. Systemic and topical administration of spermidine accelerates skin wound healing. Cell Commun Signal. 2021 Mar 22;19(1):36. doi: 10.1186/s12964-021-00717-y. PMID: 33752688; PMCID: PMC7986284.

[6] Choi, Y.H., Park, H.Y. Anti-inflammatory effects of spermidine in lipopolysaccharide-stimulated BV2 microglial cells. J Biomed Sci 19, 31 (2012). https://doi.org/10.1186/1423-0127-19-31

[7] Jeong JW, Cha HJ, Han MH, Hwang SJ, Lee DS, Yoo JS, Choi IW, Kim S, Kim HS, Kim GY, Hong SH, Park C, Lee HJ, Choi YH. Spermidine Protects against Oxidative Stress in Inflammation Models Using Macrophages and Zebrafish. Biomol Ther (Seoul). 2018 Mar 1;26(2):146-156. doi: 10.4062/biomolther.2016.272. PMID: 28365977; PMCID: PMC5839493.

[8] Kim, G., Kim, M., Kim, M. et al. Spermidine-induced recovery of human dermal structure and barrier function by skin microbiome. Commun Biol 4, 231 (2021). https://doi.org/10.1038/s42003-020-01619-4

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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