Spermidine: An anti-aging molecule with potential to reverse reproductive aging?

Spermidine is no new molecule. It has no relation to sperm, it just has an unfortunate name. It is a naturally occurring polyamine (meaning many amino acid groups) found in many common foods and has gained significant attention in recent years due to its potential health benefits. Spermidine plays a role in cellular processes including implications for aging and longevity, cognition, and more recently reproductive aging.¹ Spermidine presents a promising avenue for further research and potential therapeutic applications.

Spermidine, a polyamine characterised by its polycationic nature, is a crucial component of cellular function and homeostasis. Widely distributed in living organisms, spermidine plays a pivotal role in various biological processes, ranging from cell growth and division to DNA stability, ¹ autophagy (your body’s cellular recycling system) and improving mitochondrial function.² Recent studies have shed light on the potential health benefits associated with spermidine consumption, leading to increased interest in its therapeutic applications.

Sources of Spermidine

Spermidine is found in various food sources, including but not limited to whole grains, legumes, soybeans, and certain fruits. The human body is also capable of endogenous (make yourself) spermidine synthesis, emphasizing its fundamental role in physiological processes. As dietary intake significantly contributes to spermidine levels, understanding the sources and factors influencing its bioavailability is crucial for harnessing its potential health benefits.

Spermidine is found in various food sources, with varying concentrations. The highest food sources of spermidine include:

• Wheat Germ: Wheat germ is one of the richest sources of spermidine. It is the embryonic section of a wheat kernel and contains a concentrated amount of nutrients, including spermidine.
• Soybeans: Soybeans and soy products, such as tofu and tempeh, are rich in spermidine. These plant-based sources are not only high in spermidine but also offer other nutritional benefits.
• Mature Cheese: Certain types of mature cheeses, such as cheddar and Gouda, contain relatively high levels of spermidine. However, it's important to consider the overall nutritional profile of cheese, including its fat and salt content.
• Mushrooms: Mushrooms, particularly shiitake and white button mushrooms, contain spermidine. These fungi are not only flavorful but also contribute to the spermidine content in the diet.
• Legumes: Legumes, including lentils, chickpeas, and green peas, are good sources of spermidine. These plant-based protein sources offer a range of health benefits in addition to their spermidine content.
• Broccoli: Broccoli and other cruciferous vegetables contain spermidine. These vegetables are known for their antioxidant properties and overall health benefits.
• Spinach: Spinach is a leafy green vegetable that contains spermidine. It is a versatile ingredient that can be incorporated into various dishes.
• Mackerel and Herring: Some fatty fish, such as mackerel and herring, contain moderate levels of spermidine. These fish are also rich in omega-3 fatty acids and other nutrients.

Cellular Processes and Anti-Aging Properties

 Spermidine is intimately involved in cellular processes such as autophagy, a vital mechanism responsible for the removal of damaged cellular components. Research suggests¹ that spermidine may enhance autophagic activity, contributing to cellular rejuvenation and potentially slowing down the aging process. The anti-aging properties of spermidine have sparked interest in its potential as a longevity-promoting compound.

Reproductive Aging

Research in mice suggests that spermidine may have positive effects on reproductive aging by influencing oocyte quality, ovarian function, sperm quality, and mitochondrial function. ³However, further studies, particularly in humans, are needed to validate these findings and determine the optimal conditions for spermidine supplementation in the context of reproductive health and aging.

Cardiovascular Health

Several studies have explored the impact of spermidine on cardiovascular health. Evidence suggests that spermidine supplementation may have cardioprotective effects, including the reduction of blood pressure, improvement of vascular function, and mitigation of oxidative stress. These findings highlight spermidine's potential as a natural compound for promoting heart health and preventing cardiovascular diseases.

Neuroprotection and Cognitive Function

Spermidine has been implicated in neuroprotection and the maintenance of cognitive function. Animal studies have demonstrated that spermidine supplementation may protect against neurodegenerative diseases, enhance synaptic plasticity, and improve memory. The neuroprotective effects of spermidine raise intriguing possibilities for its role in preventing cognitive decline and age-related neurological disorders.²

Future Directions and Considerations

While the existing research on spermidine is promising, further studies are needed to elucidate its mechanisms of action and establish optimal dosage levels for various health outcomes. Spermidine is not a permissible ingredient in Australia, meaning it has not been evaluated for safety and efficacy by the Therapeutic Goods Administration.

Spermidine, a polyamine with diverse biological functions, holds promise as a natural compound with potential health benefits. From its role in cellular processes to its implications for aging, cardiovascular health, and neuroprotection, spermidine is an intriguing subject for ongoing research. There is no harm in including food sources of spermidine, in fact these are some of the healthiest foods you can eat with a multitude of additional benefits. As the scientific community continues to unravel the complexities of spermidine, it may emerge as a valuable component in promoting overall health and well-being but further research and randomised control trials are needed. 

References 

1. Ni, Y.-Q.; Liu, Y.-S. New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases. Aging Dis. 2021, 12 (8), 1948–1963. https://doi.org/10.14336/AD.2021.0603.
2. 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.; Royer, P.; Mekis, R.; Agreiter, M.; Tölle, R. C.; Sótonyi, P.; Willeit, J.; Mairhofer, B.; Niederkofler, H.; Pallhuber, I.; Rungger, G.; Tilg, H.; Defrancesco, M.; Marksteiner, J.; Sinner, F.; Magnes, C.; Pieber, T. R.; Holzer, P.; Kroemer, G.; Carmona-Gutierrez, D.; Scorrano, L.; Dengjel, J.; Madl, T.; Sedej, S.; Sigrist, S. J.; Rácz, B.; Kiechl, S.; Eisenberg, T.; Madeo, F. Dietary Spermidine Improves Cognitive Function. Cell Rep. 2021, 35 (2). https://doi.org/10.1016/j.celrep.2021.108985.
3. Zhang, Y.; Bai, J.; Cui, Z.; Li, Y.; Gao, Q.; Miao, Y.; Xiong, B. Polyamine Metabolite Spermidine Rejuvenates Oocyte Quality by Enhancing Mitophagy during Female Reproductive Aging. Nat. Aging 2023, 3(11), 1372–1386. https://doi.org/10.1038/s43587-023-00498-8.