By Andrea McBeth, ND

Welcome to our newest blog series: Metabolite of the Month.

Metabolite of the Month:
Polyamines - Spermidine & Putrescine 

Introduction

Welcome to our exploration of spermidine and putrescine, two compounds with not only intriguing names but also fascinating roles in health and longevity. I've been mulling over postbiotics for many years, poring over our metabolomics data, and contemplating the roles these molecules might play in health. Occasionally, I stumble upon classes or names that catch my attention—sometimes because of their historical context, other times because I recall a paper I read years ago that mentioned them. In the case of these compounds, they've popped up a few times in my research, but the data was often mixed or inconclusive. Yet, the subtle hints at their mechanisms always intrigued me. Like sphingolipids, they seemed to play a part in the broader orchestra of the microbial milieu. Imagine my surprise and thrill last weekend when spermidine was spotlighted at a conference alongside Thaena®. Its potential was showcased in two talks: one detailing spermidine and its class's role in autophagy—aiding in the clearance of aging cells through diet—and another tying it into the broader context of antioxidants in a skincare product line. [Shout out to Spermidine Life and Young Goose for their innovative spermidine products.] These discussions were particularly exciting to me as they are proof of a burgeoning conversation around postbiotics and offer a glimpse into how our understanding of nutrition and health is evolving, especially through the lens of the microbiome's role in transforming the foods we eat into active compounds that enhance our well-being.

What’s in a Name? The Origins of Spermidine and Putrescine

Have you ever wondered how spermidine and putrescine got their names? Just me? They might sound like they belong in a quirky science fiction novel, but their origins are deeply rooted in science. Spermidine was first isolated from semen, hence its name. Putrescine comes from a less… glamorous origin, having first been identified in decaying meats. Its name derives from the Latin word "putrescere," meaning to rot. These names not only give us a peek into their discovery stories but also make for fantastic trivia at dinner parties!

Understanding Polyamines

• Putrescine acts as a precursor in the biosynthesis pathway of other polyamines and is synthesized from the amino acid ornithine through the enzyme ornithine decarboxylase.
• Spermidine is formed from putrescine through the addition of an aminopropyl group transferred by decarboxylated S-adenosylmethionine, catalyzed by spermidine synthase.
• Spermine is synthesized from spermidine, with an additional aminopropyl group added, again facilitated by an enzyme called spermine synthase.

These polyamines are integral to cell growth and proliferation. Their levels within cells are tightly regulated through a network of transport mechanisms that ensure their balance, critical for normal cell function and preventing pathological conditions. They are involved in essential biological processes such as DNA replication, RNA transcription, protein synthesis, and post-translational modifications. These processes are crucial for cellular proliferation, differentiation, and apoptosis. In addition, many bacteria in the microbiota contain the enzyme Ornithine decarboxylase which catalyzes the decarboxylation of ornithine to form putrescine, which is a crucial step in the biosynthesis of polyamines. The production of polyamines, like putrescine, by microbiota is significant for both microbial metabolism and host interactions, including modulation of the host immune system and influencing gut health. It also serves as a significant reservoir of polyamines for the human body. 

Spermidine, Longevity, and Cognitive Support

The exploration of spermidine in the realm of longevity and cognitive enhancement is as fascinating as it is promising. Research indicates that spermidine can significantly support memory and potentially extend lifespan. Though, these studies mark just the beginning, as we continue to unravel how these molecules can support our health. 

Here are some key findings from scientific literature that elucidate spermidine’s mechanisms and potential health benefits:

• Impact on Autophagy and Aging (Study in Humans and Mice): Research published by Schroeder et al., demonstrated that spermidine promotes autophagy—a process where cells break down and recycle their own components. This mechanism is crucial for cellular rejuvenation and longevity. In human participants and mice models, spermidine supplementation was associated with increased autophagy markers and a noticeable extension in lifespan, highlighting its potential as an anti-aging nutrient.

• Cardiovascular Health (Cellular Study): A study by Nilsson et al., explored how spermidine benefits heart health. By inducing autophagy in cardiomyocytes (heart cells), spermidine helped reduce hypertension and mitigated factors leading to heart disease. This cellular-level effect underscored spermidine’s role in enhancing cardiovascular function, potentially aiding in the prevention of heart-related disorders.

• Cognitive Function and Neuroprotection (Study in Mice): In a groundbreaking study by Freitag et al., spermidine was shown to improve cognitive function in older mice. The study noted that spermidine helped maintain synaptic plasticity and memory retention, possibly through its role in modulating histone acetylation—a key process in gene expression linked to memory formation and retention.

Each of these studies contributes to a growing body of evidence that spermidine is not just a dietary supplement but a potent modulator of essential biological processes that could enhance human health significantly. As we integrate these insights into our broader understanding of postbiotics and health in general, it becomes clear that compounds like spermidine hold more potential than just being supplemental ingredients in nutritional supplements—they are powerful tools in the fight against aging and disease.

The Bigger Picture: Postbiotics and Health

Diving deeper into the world of postbiotics, compounds like polyamines stand out for their potential health impacts, particularly when our microbiomes do not provide an adequate reservoir for normal cellular processes. The scientific community’s growing interest in molecules that were traditionally not connected to the microbiome but can now be connected to dietary intake of precursors is fascinating. I expect the connection of foundational molecules like these that are also postbiotics will continue to reveal their roles in health maintenance, reshaping our understanding of how microbially derived metabolites can significantly influence our well-being. It's an exciting time as we explore these new frontiers and examine how these small but mighty molecules can play more substantial roles in the broader context of health and disease.

Conclusion

To wrap up, the world of dietary polyamines and the microbiome’s role in transforming these compounds underscores a promising frontier in health research. As we continue to collect both scientific and anecdotal evidence at Thaena®, the contributions of compounds found in products like ThaenaBiotic® become increasingly significant. It is a testament to the power of combining nature, science, and innovation to forge new paths in our understanding and management of health. The intricate relationship between dietary polyamines, the microbiome, and our overall well-being not only highlights the complexity of our biological systems but also points towards the immense potential of leveraging these interactions for therapeutic advancements. As we continue to unlock the secrets held by these microscopic interactions, we may find more natural ways to enhance our health, prevent diseases, and perhaps even extend our lives. 

It is clear that the future of health might just lie in the hidden details of our body's interaction with the smallest parts of nature. By nurturing our microbiome and understanding its profound impact on our health through components like polyamines, we are stepping into a new era of bio-enhanced medicine where every meal and every microbe counts.

References

1. Zou, D., Zhao, Z., Li, L., Min, Y., Zhang, D., Ji, A., Jiang, C., Wei, X., & Wu, X. (2022). A comprehensive review of spermidine: Safety, health effects, absorption and metabolism, food materials evaluation, physical and chemical processing, and bioprocessing. Comprehensive Reviews in Food Science and Food Safety, 21(3), 2820–2842. https://doi.org/10.1111/1541-4337.12963

2. Madeo, F., Eisenberg, T., Pietrocola, F., & Kroemer, G. (2018). Spermidine in health and disease. Science, 359(6374). https://doi.org/10.1126/science.aan2788

3. Xuan, M., Gu, X., Li, J., Huang, D., Xue, C., & He, Y. (2023). Polyamines: their significance for maintaining health and contributing to diseases. Cell Communication and Signaling: CCS, 21(1), 348. https://doi.org/10.1186/s12964-023-01373-0 

4. Schroeder, S., Hofer, S. J., Zimmermann, A., Pechlaner, R., Dammbrueck, C., Pendl, T., Marcello, G. M., Pogatschnigg, V., Bergmann, M., Müller, M., Gschiel, V., Ristic, S., Tadic, J., Iwata, K., Richter, G., Farzi, A., Üçal, M., Schäfer, U., Poglitsch, M., … Madeo, F. (2021). Dietary spermidine improves cognitive function. Cell Reports, 35(2), 108985. https://doi.org/10.1016/j.celrep.2021.108985

5. Nilsson, B.-O., & Persson, L. (2019). Beneficial effects of spermidine on cardiovascular health and longevity suggest a cell type-specific import of polyamines by cardiomyocytes. Biochemical Society Transactions, 47(1), 265–272. https://doi.org/10.1042/BST20180622

6. Freitag, K., Sterczyk, N., Wendlinger, S., Obermayer, B., Schulz, J., Farztdinov, V., Mülleder, M., Ralser, M., Houtman, J., Fleck, L., Braeuning, C., Sansevrino, R., Hoffmann, C., Milovanovic, D., Sigrist, S. J., Conrad, T., Beule, D., Heppner, F. L., & Jendrach, M. (2022). Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model. Journal of Neuroinflammation, 19(1), 172. https://doi.org/10.1186/s12974-022-02534-7