Spermidine

Spermidine is a polyamine compound found in living tissues and is known for its role in cellular function and development. It has been increasingly recognized for its potential health benefits, particularly concerning longevity and age-related diseases. Studies have indicated that spermidine has the ability to promote autophagy, the body's intracellular recycling mechanism, which is crucial for cellular maintenance, homeostasis, and overall health. Spermidine is a naturally occurring biogenic polyamine, synthesized from the amino acid ornithine through the action of the enzyme ornithine decarboxylase (ODC). It is involved in various fundamental biological processes, including DNA stability, RNA transcription, translation, enzyme function, and cell proliferation. As a cellular polyamine, spermidine is essential for both normal and neoplastic tissue growth and is found in all eukaryotic cells.

Dietary Sources

Spermidine is present in a wide variety of foods. Rich dietary sources of spermidine include:

Sources

Good dietary sources of spermidine are aged cheese, mushrooms, soy products, legumes, corn, and whole grains. Spermidine is plentiful in a Mediterranean diet. For comparison: The spermidine content in human seminal plasma varies between approx. 15 and 50 mg/L (mean 31 mg/L).

Food	Spermidine mg/kg	notes & refs
Wheat germ	243
Soybean, dried	207	Japanese
Cheddar, 1yr old	199
Soybean, dried	128	German
Mushroom	89	Japanese
Rice bran	50
chicken liver	48
Green peas	46
Mango	30
Chickpea	29
Cauliflower (cooked)	25
Broccoli (cooked)	25

Note - spermidine content varies by source and age. See ref for details.

In grains, the endosperm contains most of the spermidine. One of the best known grain dietary sources is wheat germ, containing as much as 243 mg/kg.

Considering a balanced diet that includes these foods can increase spermidine intake, which, in light of recent research, could be beneficial for health and longevity.

Spermidine and Longevity

Research has identified a significant correlation between the exogenous supplementation of spermidine and increased lifespan in several model organisms such as yeast, worms, flies, and mice. The longevity-promoting properties of spermidine are primarily attributed to its role in inducing autophagy.

Autophagy

Autophagy is a cellular process involved in the degradation and recycling of obsolete or dysfunctional cellular components. This mechanism is vital for maintaining cellular homeostasis and plays a central role in cell and tissue health. Spermidine's ability to enhance autophagy is of particular interest in the context of aging, as the decline in autophagy has been associated with several age-related pathologies, including neurodegeneration, cardiovascular disease, and cancer.

Spermidine promotes autophagy through the inhibition of the acetyltransferase EP300, leading to hypolysine acetylation of the protein eIF5A, among other targets, and consequently inducing autophagic processes. The upregulation of autophagy is believed to alleviate the phenotypic characteristics of aging within cells, thus promoting cellular longevity.

Cardiovascular Health

Apart from its role in autophagy, spermidine has been observed to contribute to cardiovascular health. Dietary spermidine intake is linked to reduced blood pressure and decreased risk of heart disease, potentially due to its ability to induce autophagy in cardiac myocytes, thus preventing the onset of heart failure and other related conditions.

Safety and Dosage

While spermidine supplementation appears to be safe at physiological doses, the optimal dosage for human health and longevity outcomes remains unclear. Most of the current data on spermidine's health benefits come from animal studies, and more comprehensive clinical trials are needed to determine effective dosing strategies for humans.

Current Research and Future Directions

Ongoing research on spermidine is exploring its potential benefits in neuroprotective therapy, especially concerning age-related diseases like Alzheimer's and Parkinson's, given the role of autophagy in neurodegenerative conditions. Furthermore, as understanding of the molecular mechanisms linking spermidine and autophagy deepens, there is increasing interest in the potential application of spermidine in therapies for various diseases and in general health maintenance.

The burgeoning field of longevity science continues to investigate spermidine and other autophagy-inducing compounds as potential interventions for aging and associated pathologies. Future clinical trials in humans will be crucial for validating spermidine's efficacy and establishing therapeutic protocols.