Spermidine

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Structural formula
Structural formula of spermidine
General
Surname Spermidine
other names
  • Monoaminopropylputrescine
  • 1,5,10-triazadecane
  • N - (3-aminopropyl) butane-1,4-diamine ( IUPAC )
Molecular formula C 7 H 19 N 3
Brief description

colorless, clear liquid

External identifiers / databases
CAS number 124-20-9
EC number 204-689-0
ECHA InfoCard 100.004.264
PubChem 1102
ChemSpider 1071
DrugBank DB03566
Wikidata Q418834
properties
Molar mass 145.25 g mol −1
Physical state

liquid

density

0.93 g cm −3

Melting point

22-25 ° C

safety instructions
GHS labeling of hazardous substances
05 - Corrosive

danger

H and P phrases H: 314
P: 280-305 + 351 + 338-310
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Spermidine , also known as monoaminopropylputrescine , is a biogenic polyamine and an intermediate in the formation of spermine from putrescine and decarboxylated S- adenosylmethionine .

Spermidine is found in all living organisms and is closely related to cell growth. The exact physiological function of spermidine in growing cells , e.g. B. in the production of nucleic acids and proteins or membrane stabilization, but has not yet been fully clarified. The amount of spermidine in the organism increases with an acceleration of the metabolism . When the metabolism slows down, the production of spermidine decreases. The concentration of the body's own spermidine also decreases with aging .

Natural circumstances that cause the spermidine level to rise are growth , pregnancy , the repair of muscle cells after strenuous exercise and the regeneration of red blood cells after blood loss or poverty or after prolonged stays at high altitude. Various diseases are also signaled by increased spermidine levels, e.g. B. chronic inflammation of the joints (“ rheumatism ”), the liver ( hepatitis ), the intestines ( colitis ) and the skin ( eczema , psoriasis ).

Heart protection, dementia prophylactic effect, reduced mortality risk and reduced coronavirus replication in cell experiments

Spermidine has a reinforcing effect on autophagy , a cellular process that is crucial for the general cell activity of proteins as well as the function of mitochondria and cardiomyocytes (heart muscle cells) . Animal experiments on fruit flies had shown that feeding these insects with spermidine counteracts age-related dementia . (Original article) A research group led by the Graz molecular biologist Frank Madeo succeeded in demonstrating in laboratory mice that spermidine protects against cardiovascular diseases and can thus contribute to extending life. It delays cardiac aging by improving diastolic function . Animal experiments have shown that hypertension , a major cause of heart failure , is reduced by spermidine. Spermidine reduced the pulmonary or systemic accumulation of fluid, which is characteristic of heart failure. The tests also revealed a protective effect on kidney function. The consumption of spermidine in an appropriate diet correlated inversely with the incidence of heart failure. In the study groups (high and low intake), the risk of disease in the high intake group was reduced by 40 percent.

In August 2018, Austrian, French and English clinicians and researchers published the results of a twenty-year clinical observation period (1995-2015), during which the intake of spermidine in the eating habits of a group of people was regularly recorded. 829 people between 45 and 84 years old (49 percent male) took part in the study. During this period, 341 of the people died, 40.5 percent of them in the lower third of the spermidine intake, 24 percent in the middle and 15 percent in the upper third. The different mortality risk of people in the upper third compared to that of the lower third corresponded to an age 5 to 7 years lower. 

Frank Madeo received the Seneca Medal 2019, a renowned research award, on April 9, 2019 for his groundbreaking research, which over a period of 20 years has led from fundamental mechanistic investigations in single cells to practical concepts of aging prevention and intervention in humans of the Industrie-Club Düsseldorf in connection with the Erwin-Niehaus-Foundation.

In cell experiments, virologists from the Charité Berlin headed by Christian Drosten and Marcel Müller were able to show that human lung cells infected with SARS-CoV-2 had reduced autophagy. In addition, the spermidine levels in these cells were significantly reduced. By administering spermidine, it was finally possible to influence the infection. The viral load was reduced by 85% after administration of the endogenous substance.

The researchers were also able to show that healthy cells that had previously been treated with spermidine were clearly protected from infection. Virus replication was reduced by 70% in these cells. The authors of the study conclude that this will result in new research approaches for both therapy and prevention. So far, however, there are no meaningful studies on humans, and it is not known whether effective tissue concentrations can be achieved in practice by the oral intake of spermidine.

Human medicine and autophagy experts exchanged views on the therapeutic potential of spermidine in a joint meeting in November 2019. It was agreed that the findings from animal studies and initial studies on humans open up interesting medical perspectives for spermidine. Starting spermidine supplementation early in middle age might be an option to benefit from the effects in the long term. However, before a concrete therapeutic potential for spermidine can be derived, further investigations are required. An active recommendation in everyday practice is not yet possible based on the current data situation.

Tolerability and side effects

In a three-month phase II study with a plant extract that was rich in spermidine, a dose of 1.2 mg per day was found to be well tolerated in older cognitively impaired people. In comparison, in the color mouse animal model, the doses at which an autophagy-stimulating effect could be measured are 50 mg / kg body weight and intraperitoneal administration. This effect was much less pronounced at a tenth of the dose.

So far there is no approved drug based on the active ingredient spermidine.

Biochemical and physiological effects

Occurrence in food

Foods with a high spermidine content are whole grains or wheat germ, aged cheese, mushrooms, soy products and legumes.

For comparison: the spermidine content in human seminal plasma (cell-free ejaculate ) is 15 to 50 mg / L (mean value 31 mg / L).

food Spermidine
mg / kg		 Remarks
Wheat germ 243
Soybeans , dried 207 Japan
Cheddar cheese , matured for 1 year 199
Soybeans, dried 128 Germany
Pumpkin seeds 104 Austria
Mushrooms 89 Japan
Rice bran 50
Chicken liver 48
Peas 46
Minced meat, beef 37
Corn 32
mango 30th
Chickpeas 29
dill 29
celery 27
Cauliflower (cooked) 25th
Broccoli (cooked) 25th
Hazelnuts 21st
Lettuce 19th
okra 19th
Whole grain bread 18th
spinach 16
melon 12

Spermidine in the media

literature

Individual evidence

  1. ↑ a b c d e f sheet spermidine at Sigma-Aldrich , accessed on 23 April 2011 ( PDF ).
  2. ↑ Kazuei Igarashi, Keiko Kashiwagi: Modulation of cellular function by polyamines. In: The International Journal of Biochemistry & Cell Biology. 42, 2010, p. 39, doi : 10.1016 / j.biocel.2009.07.009 .
  3. ↑ S. Mandal, A. Mandal, HE Johansson, AV Orjalo, MH Park: Depletion of cellular polyamines, spermidine and spermine, causes a total arrest in translation and growth in mammalian cells. In: Proceedings of the National Academy of Sciences. 110, 2013, p. 2169, doi : 10.1073 / pnas.1219002110 .
  4. ↑ a b Administration of the natural substance spermidine stops dementia. Freie Universität Berlin, September 1, 2013, accessed on September 4, 2013 .
  5. ↑ Frank Madeo et al .: Induction of autophagy by spermidine promotes longevity . In: US National Library of Medicine National Institutes of Health (Ed.): Nat Cell Biol . November 11, 2009, p. 1305-1314 , doi : 10.1038 / ncb1975 , PMID 19801973 .
  6. ↑ Varun K Gupta, Lisa Scheunemann, Tobias Eisenberg, Sara Mertel, Anuradha Bhukel, Tom S Koemans, Jamie M Kramer, Karen SY Liu, Sabrina Schroeder, Hendrik G Stunnenberg, Frank Sinner, Christoph Magnes, Thomas R Pieber, Shubham Dipt, André Fiala, Annette Schenck, Martin Schwaerzel, Frank Madeo, Stephan J Sigrist: Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner . In: Nature Neuroscience . 2013, doi : 10.1038 / nn.3512 (English).
  7. ↑ Frank Madeo et al .: Cardioprotection and lifespan extension by the natural polyamine spermidine . In: Nat Med . December 22, 2016, p. 1428-1438 , doi : 10.1038 / nm.4222 , PMID 27841876 .
  8. ↑ S. Kiechl, R. Pechlaner, P. Willeit et al .: Higher spermidine intake is linked to lower mortality: a prospective population-based study . In: The American Journal of Clinical Nutrition . tape 108 , no. 2 , August 1, 2018, p. 371-380 , doi : 10.1093 / ajcn / nqy102 , PMID 29955838 .
  9. ↑ SENECA-MEDAL 2019. INDUSTRIE-CLUB DÜSSELDORF, May 8, 2019, accessed on May 15, 2019 .
  10. ↑ Gerhild Leljak: Seneca Medal for molecular biologists Frank Madeo. University of Graz, May 9, 2019, accessed on May 15, 2019 .
  11. ↑ a b Nils C. Gassen, Christian Drosten, Marcel A. Müller et. al .: Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics . In: BioRxiv . April 15, 2020, bioRxiv : 10.1101 / 2020.04.15.997254v1 ( preprint full text).
  12. ↑ [1]
  13. ↑ Martin Smollich: Charité study: With spermidine against COVID-19. In: Nutritional Medicine. April 23, 2020, accessed on April 23, 2020 (German).
  14. ↑ Expert board autophagy inducers "Spermidine and fasting". In: spermidin.health. Retrieved on May 11, 2020 (German).
  15. ↑ C. Schwarz, S. Stekovic et al. a .: Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline. In: Aging. Volume 10, number 1, January 2018, pp. 19–33, doi : 10.18632 / aging.101354 , PMID 29315079 , PMC 5807086 (free full text).
  16. ↑ E. Morselli, G. Mariño et al. a .: Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. In: Journal of Cell Biology . Volume 192, number 4, February 2011, pp. 615-629, doi : 10.1083 / jcb.201008167 , PMID 21339330 , PMC 3044119 (free full text).
  17. ^ S. Wang, S. Joshi, S. Lu: Delivery of DNA to skin by particle bombardment. In: Methods in molecular biology. Volume 245, 2004, pp. 185-196, PMID 14707379 .
  18. ↑ a b c d e f g h i j k l Mohamed Atiya Ali, Eric Poortvliet, Roger Strömberg, Agneta Yngve: Polyamines in foods: development of a food database . In: Food & Nutrition Research . tape 55 , no. 1 , January 1, 2011, p. 5572 , doi : 10.3402 / fnr.v55i0.5572 , PMID 21249159 , PMC 3022763 (free full text).
  19. ↑ semen . In: Ciba-Geigy (Ed.): Scientific tables Geigy . 8th edition. Partial volume of body fluids. CIBA-GEIGY Limited, Basel 1977, p. 181-189 .
  20. ↑ TM Klein, T. Gradziel, ME Fromm, JC Sanford: Factors Influencing Gene Delivery into Zea Mays Cells by High-Velocity Microprojectiles . In: Nature Biotechnology . tape 6 , no. 5 , p. 559-563 , doi : 10.1038 / nbt0588-559 .
  21. ↑ Spermidine miracle pumpkin seed. Retrieved September 30, 2019 (German).
  22. ↑ a b c d e f g h i j spermidine foods. Accessed April 15, 2019 (German).