I am deeply grateful to our sponsors who enable my team and me to devote our energy and time to writing, research, and education. Each company that sponsors us is one that I personally trust for myself, my patients, and my fellow practitioners. I encourage you to check out their websites and see the incredible work they’re doing! -Dr. Tom
Confronted with age and mortality, humans have sought youthfulness for thousands of years. The first mention of the fountain of youth, for example, appears in the writings of Herodotus in the 5th Century BC. Still searching, we are now aided by modern science, commerce, and geography (I think we can all agree that Ponce de Leon did not find the fountain of youth in Florida). With the help of all three, the search is over: you can find and buy spermidine. Bonus if that spermidine is sourced in Japan (more on this later).
What is Spermidine?
Spermidine is a polyamine produced in every cell in the body and by your gut microbiota, but the body supplements its levels with polyamines found in food. After a few hundred years of research—it was discovered in the 1600s by microscopy pioneer Antoni Van Leeuwenhoek—we now know spermidine has many health-giving effects including “anti-inflammatory properties, antioxidant functions, enhancement of mitochondrial metabolic function and respiration, as well as improved proteostasis and chaperone activity” [1].
It is classified as a caloric restriction mimetic or a substance that mimics the beneficial effects of caloric restriction or fasting, “among the few regimens known to extend life and beneficially affect health in all tested model organisms” [2]. Crucially for its anti-aging effects, it’s an inducer of autophagy, a cellular process that collects and degrades cellular trash thereby maintaining and promoting homeostasis.
Spermidine & the Hallmarks of Aging
In a landmark paper by Lopez-Otin and its more recent update, the ‘hallmarks of aging’ or pathways through which we age, at least at the cellular level, were defined [3]. Among the 12 hallmarks are stem cell exhaustion, mitochondrial dysfunction, gut dysbiosis, and inflammation. It turns out that for most of the hallmarks, activating autophagy can prevent or slow their progression. For example, stem cell decline emerges (in number and function) as the consequence of multiple types of cell damage—other hallmarks like genomic instability and mitochondrial dysfunction—and overuse or “exhaustion.” Spermidine plays a key part in stabilizing DNA for transcription and translation and inducing autophagy to clear aberrant mRNAs, misfolded proteins, and nonfunctional mitochondria [1]. As a result, the negative impacts of all three hallmarks are lessened.
A paper currently under review makes the case that spermidine actually slows all of the hallmarks, at least in some organs like the lungs, though its positive effects have been confirmed in vitro for nine of the 12. This is due to its many effects and upregulation of genes key to autophagy such as Beclin-1, transcription factor TFEB, and translation initiation factor eIF5A [4].
Spermidine & Autophagy
One of the most significant mechanisms of spermidine, since it impacts nearly all of the Hallmarks of Aging, is its role in promoting autophagy. Autophagy is like the body’s internal recycling program, where cells break down and remove damaged components, making way for new, healthy ones. This process is vital for maintaining cellular health and function.
As we age, autophagy becomes less efficient, leading to an accumulation of cellular debris that can contribute to various diseases, including neurodegenerative conditions and cancer. Spermidine has been shown to induce autophagy, effectively giving your cells a helping hand in keeping themselves clean and functional.
Spermidine & Visible Benefits
The impacts of aging more readily visible than, say, mitochondrial dysfunction, are also impacted by spermidine. For example, spermidine has been found to enhance hair growth, sleep, and cognition, all known to worsen with aging.
Spermidine & Hair Growth
Spermidine plays two distinct parts in promoting hair growth. First, polyamines are directly required to move hair follicles into the growth phase (also known as the anagen phase). Second, and more indirectly, spermidine induces autophagy, which is required for both the rescue of resting hair follicles and the proper functioning of hair follicle stem cells, which generate new cells that can grow hair follicles [5]. Supplementing with spermidine then can mean your body generates more hair follicles and that more of these follicles are in the growth phase.
Spermidine & Skin Health
Spermidine’s benefits extend to the skin, where it supports cellular regeneration and reduces oxidative stress. This can lead to improved skin elasticity, reduced wrinkles, and a more youthful appearance.
Research suggests that spermidine promotes the production of collagen, a protein essential for skin structure and elasticity. It also helps in protecting the skin from damage caused by UV radiation and other environmental stressors. So, in a way, spermidine might just be your new secret weapon for glowing, healthy skin [6].
Spermidine & Internal Benefits
Spermidine & Sleep
Circadian rhythms influence important functions in our bodies, including our sleep patterns. It turns out that in model organisms like mice, clock genes (that direct the circadian rhythm) and polyamines regulate each other. As polyamine levels fall, the circadian period lengthens. But, restoring polyamine levels, even a single pulse of spermidine, can restore and reset the circadian clock [7]. While these findings have not yet been replicated in humans, the suggestion that our body’s rhythm and restful sleep could be achieved by spermidine supplementation is an exciting prospect.
Spermidine, Memory & Cognition
Like humans, many organisms experience age-dependent memory impairment including common animal models like Drosophila (flies) and mice. By feeding flies spermidine, researchers were able to restore polyamine levels and suppress age-induced memory impairment [8]. Their findings also name autophagy, as induced by spermidine, as the mechanism by which memory formation is rescued. These findings are supported by many other animal studies that have found that the administration of polyamines to animals improves memory in most learning and memory tasks.
Spermidine & Cardiovascular Health
Your heart and blood vessels could also benefit from spermidine. Research indicates that higher dietary intake of spermidine is associated with reduced risk of cardiovascular diseases. This connection is likely due to spermidine’s ability to improve endothelial function (the health of the cells lining blood vessels) and reduce inflammation.
In animal studies, spermidine has been shown to extend lifespan and improve cardiovascular health markers, such as blood pressure and arterial elasticity [9]. These promising findings suggest that incorporating spermidine-rich foods into your diet could be a simple yet effective strategy for maintaining heart health.
Spermidine, Energy & Metabolism
Metabolic health is another area where spermidine shines. It plays a role in regulating metabolism and maintaining mitochondrial function – the powerhouses of our cells [10]. Efficient mitochondria are crucial for energy production and overall metabolic health.
Spermidine has been shown to improve insulin sensitivity and reduce the risk of metabolic disorders like type 2 diabetes [11]. By supporting cellular metabolism and energy production, spermidine helps keep your body’s engine running smoothly, potentially aiding in weight management and overall vitality.
Spermidine & Immunity
A robust immune system is the cornerstone of good health, and spermidine can give it a boost. By promoting autophagy, spermidine helps in the removal of damaged cells and pathogens, thereby supporting a more efficient immune response.
Studies have shown that spermidine supplementation can enhance the function of immune cells, such as T-cells, which play a crucial role in defending against infections and diseases [12]. With a stronger immune system, your body is better equipped to handle the challenges of everyday life and stay resilient against illnesses.
Increasing Spermidine Intake
Now that you’re convinced that you need more spermidine in your diet, you may be asking how? Spermidine is found in many foods such as aged cheeses, peas, shiitake mushrooms, and wheat germ. Though, if we had to incorporate one spermidine-rich food into our diet daily, we would do what the long-lived Okinawans do and eat their version of natto, a Japanese delicacy and a long-fermented soybean concoction that has the highest spermidine content by weight. The Okinawan version is fermented for one year in limestone caves. (That’s an anti-aging secret right there!) Unfortunately, it is time-consuming to make (with or without a cave) and hard to find (depending on where you live); additionally, it has a unique smell, texture, and taste that can put off even the hardiest of longevity enthusiasts.
Oxford Healthspan’s Primeadine, the Highest Quality Spermidine Supplement on the Market
If consuming 50 to 100 g of natto is not in the cards for you, spermidine levels can be maintained through supplements. Given Japanese scientific authority on autophagy–the mechanism of action for autophagy was discovered by Japanese scientist Ohsumi Yoshinori– combined with their historic love of a variety of spermidine-rich foods, Japan is an obvious place to look.
There are a few spermidine supplements on the market, but we believe Primeadine, by Oxford Healthspan, is the best. This premium spermidine supplement is carefully extracted from wheat germ in Japan using a precisely controlled drying method. We know this sourcing is important because food-grade spermidine is more bioavailable and recognized by the body. The formulation also includes polyamines spermine and putrescine, which only increases its efficacy.
We are also committed to the highest quality manufacturing possible. Oxford Healthspan’s supplier, for example, is one of 150 companies in Japan to be both ISO22000 certified and Good Manufacturing Practices certified (cGMP) by the Japan Institute for Health Food Standards (JIHFS). The product is tested once in Japan and again tested by a third party for purity and heavy metals in the United States. It’s encapsulated in a Good Manufacturing Practices (GMP)-certified plant in the US using vegan capsules. On top of all this, Primeadine® is free from fillers and flow agents, talc, shellac, or any other synthetic ingredients, and has the potentially rancid omega-6 fatty acids found in wheat germ removed – as pure as it gets.
Spermidine: The Encapsulated Fountain of Youth
Based on its longevity and health-restoring effects, I’d bet that Herodotus, Ponce de Leon, and most living longevity enthusiasts would agree that spermidine effectively ends the search for the fountain of youth. And, because it’s naturally produced by the body, restoring youthful levels of spermidine is well-tolerated by the body. There will be no side effects from adding more spermidine to your diet, particularly if it’s in the form of Primeadine. Order your spermidine supplements and reap the rewards today!
Interested in learning more about Spermidine?
References
- Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018). Spermidine in health and disease. Science, 359(6374).
- Singh S, Kumar R, Garg G, Singh AK, Verma AK, Bissoyi A, Rizvi SI. 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. Biogerontology. 2021 Feb;22(1):35-47. doi: 10.1007/s10522-020-09900-z. Epub 2020 Sep 26. PMID: 32979155.
- López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023). Hallmarks of aging: An expanding universe. Cell, 186(2), 243-278. https://doi.org/10.1016/j.cell.2022.11.001
- Kaushik, S., Tasset, I., Arias, E., Pampliega, O., Wong, E., Martinez-Vicente, M., & Cuervo, A. M. (2021). Autophagy and the Hallmarks of Aging. Ageing Research Reviews, 72, 101468. https://doi.org/10.1016/j.arr.2021.101468.
- Ramot, Y., Tiede, S., Bíró, T., Abu Bakar, M. H., Sugawara, K., Philpott, M. P., Harrison, W., Pietilä, M., & Paus, R. (2011). Spermidine promotes human hair growth and is a novel modulator of human epithelial stem cell functions. PloS one, 6(7), e22564.
https://doi.org/10.1371/journal.pone.0022564 - Kim, G., Kim, M., Kim, M., Park, C., Yoon, Y., Lim, D., Yeo, H., Kang, S., Lee, Y., Beak, N., Lee, J., Kim, S., Kwon, J. Y., Choi, W. W., Lee, C., Yoon, K. W., Park, H., & Lee, D. (2021). Spermidine-induced recovery of human dermal structure and barrier function by skin microbiome. Communications Biology, 4(1), 1-11.
https://doi.org/10.1038/s42003-020-01619-4 - Yang, D., Oike, H., Furuse, M., & Yasuo, S. (2021). Spermidine resets circadian clock phase in NIH3T3 cells. Biomedical research (Tokyo, Japan), 42(5), 221–227.
https://doi.org/10.2220/biomedres.42.221 - Schwarz C, Benson GS, Horn N, et al. Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial. JAMA Netw Open. 2022;5(5):e2213875. doi:10.1001/jamanetworkopen.2022.13875
- Navas, P. (2016). Spermidine to the rescue for an aging heart. Nature Medicine, 22(12), 1389. https://doi.org/10.1038/nm.4243
- Muna Al-Habsi et al., Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice.Science378,eabj3510(2022).DOI:10.1126/science.abj3510
- Liao, Y., P Kummert, O. M., Bair, A. M., Alavi, N., Alavi, J., Miller, D. M., Bagga, I., Schempf, A. M., Hsu, M., Brown Mayfield, S. M., Mitchell, A. N., Tannady, G., Talbot, A. R., Dueck, A. M., Ovando, R. B., Parker, H. D., Wang, J., Schoeneweis, J. K., & Kennedy, B. K. (2021). The Autophagy Inducer Spermidine Protects Against Metabolic Dysfunction During Overnutrition. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 76(10), 1714-1725. https://doi.org/10.1093/gerona/glab145
- Chamoto, K., Zhang, B., Tajima, M., Honjo, T., & Fagarasan, S. (2024). Spermidine – an old molecule with a new age-defying immune function. Trends in cell biology, 34(5), 363–370. https://doi.org/10.1016/j.tcb.2023.08.002
