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
Good dietary sources of spermidine are aged cheese, mushrooms, soy products, legumes, corn, and whole grains.[1] Spermidine is plentiful in a Mediterranean diet.[2]
For comparison: The spermidine content in human seminal plasma varies between approx. 15 and 50 mg/L (mean 31 mg/L).[3]
| Food | Spermidine
mg/kg |
notes & refs |
|---|---|---|
| Wheat germ | 243 | [4] |
| Soybean, dried | 207 | Japanese [1] |
| Cheddar, 1yr old | 199 | [1] |
| Soybean, dried | 128 | German [1] |
| Mushroom | 89 | Japanese [1] |
| Rice bran | 50 | [1] |
| chicken liver | 48 | [1] |
| Green peas | 46 | [1] |
| Mango | 30 | [1] |
| Chickpea | 29 | [1] |
| Cauliflower (cooked) | 25 | [1] |
| Broccoli (cooked) | 25 | [1] |
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[5].
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 a specific enzyme called acetyltransferase EP300. This inhibition leads to a series of cellular events that eventually increase the autophagic processes within the cells. Essentially, spermidine helps in "cleaning up" the cell interiors, which is crucial for cellular maintenance and health, especially as the body ages[6].
Cardiovascular Health
Apart from its role in autophagy, spermidine has been observed to contribute to cardiovascular health. A study demonstrated that oral supplementation of spermidine (as well as spermine) extended the lifespan of mice and exerted cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Moreover, spermidine feeding enhanced cardiac autophagy, mitophagy, and mitochondrial respiration, also improving the mechano-elastical properties of cardiomyocytes in vivo. In a model of hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. High levels of dietary spermidine in humans, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease[5].
Bioavailability
In a randomized controlled trail [7] 15 mg/d of spermidine was administered orally in 12 healthy volunteers for 5 days and the blood levels of spermidine and two related compounds, spermine and putrescine, were measured. Only spermine blood levels increased significantly, but no effect on spermidine or putrescine could be detected. That suggests, when spermidine is taken orally as a supplement, it gets converted into spermine before it enters the bloodstream. This conversion happens presystemically, meaning it occurs before spermidine gets into the systemic circulation. This suggest that the bioavailability of spermidine, in its original form, might be low or perhaps altered, but the compound is still bioavailable in a different form (as spermine) which then has systemic effects.
The study also found that a daily dose of 15 mg of spermidine was needed to see a significant increase in spermine levels in the blood. Lower doses like 0.9-1.2 mg of spermidine per day didn't show changes in blood levels of spermidine, spermine or putrescine. This suggests that there's a certain amount of spermidine you need to take to see an effect.
Safety and Dosage
Safety
A 3-month randomized, placebo-controlled, double-blind Phase II trial conducted on older adults with subjective cognitive decline demonstrated that a daily dose of 1.2 mg spermidine was safe and well-tolerated, with no significant differences in vital signs, weight, and clinical chemistry observed between the spermidine and placebo-treated groups[8].
Dosage
The optimal dosage for human health and longevity outcomes remains unclear.
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Ali et al.; "Polyamines in foods: development of a food database" , https://doi.org/10.3402/fnr.v55i0.5572
- ↑ Madeo F, Eisenberg T, Pietrocola F, Kroemer G; "Spermidine in health and disease" , https://doi.org/10.1126/science.aan2788
- ↑ Ciba-Geigy, ed. (1977), "Sperma", Wissenschaftliche Tabellen Geigy (in German) (8 ed.), Basel: CIBA-GEIGY Limited, vol. Teilband Körperflüssigkeiten, pp. 181-189
- ↑ Brochure on Polyamines, rev. 2, http://www.oryza.co.jp/html/english/pdf/polyamine_vol.2.pdf
- ↑ 5.0 5.1 Eisenberg T, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016 Dec;22(12):1428-1438. doi: 10.1038/nm.4222. Epub 2016 Nov 14. PMID: 27841876; PMCID: PMC5806691.
- ↑ Pietrocola F, et al. Spermidine induces autophagy by inhibiting the acetyltransferase EP300. Cell Death Differ. 2015 Mar;22(3):509-16. doi: 10.1038/cdd.2014.215. Epub 2014 Dec 19. PMID: 25526088; PMCID: PMC4326581.
- ↑ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143675/
- ↑ Schwarz C, et al. Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline. Aging (Albany NY). 2018 Jan 8;10(1):19-33. doi: 10.18632/aging.101354. PMID: 29315079; PMCID: PMC5807086.