Spermidine: Difference between revisions

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'''Spermidine''' or '''spermidin''' or C7H19N3 is a natural component of our cells that is found in sperm, different fruits and vegetables, meat, and cheese.<ref name="PubChem">https://pubchem.ncbi.nlm.nih.gov/compound/spermidine</ref><ref name="DrugBank"/> Spermidine is essential for healthy [[metabolism]] in humans.<ref name="Zheng2022"/> Two-thirds of the spermidine levels in humans are maintained through eating a [[healthy, balanced diet]] combined with certain bacteria in the [[digestive tract]], the remaining third of the spermidine is produced by the body's own cells.<ref name="Edzard2020">https://edzardernst.com/2020/05/spermidine-the-new-wonder-supplement-sadly-not/</ref><ref name ="Madeo2018">https://www.science.org/doi/10.1126/science.aan2788</ref>  
'''Spermidine''' or '''spermidin''' or C7H19N3 is a natural component of our cells that is found in sperm, different fruits and vegetables, meat, and cheese.<ref name="PubChem">{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/1102|title=Spermidine|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=PubChem|language=en|archive-url=|archive-date=|url-status=|access-date=2022-06-30}}</ref><ref name="DrugBank" /> Spermidine is essential for healthy [[metabolism]] in humans.<ref name="Zheng2022" /> Two-thirds of the spermidine levels in humans are maintained through eating a [[healthy, balanced diet]] combined with certain bacteria in the [[digestive tract]], the remaining third of the spermidine is produced by the body's own cells.<ref name="Edzard2020">{{Cite web|url=https://edzardernst.com/2020/05/spermidine-the-new-wonder-supplement-sadly-not/|title=Spermidine, the new ‘wonder supplement’? SADLY NOT!|last=Ernst|first=Edzard|authorlink=|last2=|first2=|authorlink2=|date=2020-05-27|website=edzardernst.com|language=en-GB|archive-url=|archive-date=|url-status=|access-date=2022-06-30}}</ref><ref name="Madeo2018">{{Cite journal|title=Spermidine in health and disease|date=2018-01-26|url=https://www.science.org/doi/10.1126/science.aan2788|journal=Science|volume=359|issue=6374|pages=eaan2788|last=Madeo|first=Frank|last2=Eisenberg|first2=Tobias|last3=Pietrocola|first3=Federico|last4=Kroemer|first4=Guido|language=en|doi=10.1126/science.aan2788|issn=0036-8075}}</ref>  


Spermidine is a polyamine found in almost all tissues in association with nucleic acids and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine.<ref name="DrugBank">https://www.drugbank.ca/drugs/DB03566</ref>
Spermidine is a polyamine found in almost all tissues in association with nucleic acids and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine.<ref name="DrugBank">{{Cite web|url=https://go.drugbank.com/drugs/DB03566|title=Spermidine|last=|first=|authorlink=|last2=|first2=|authorlink2=|date=|website=DrugBank|archive-url=|archive-date=|url-status=|access-date=2022-06-30}}</ref>


==Sources ==
==Sources ==
The main sources of spermidine in humans are plant- and fungal-derived products are the most relevant sources of spermidine, especially:
The main sources of spermidine in humans are plant- and fungal-derived products are the most relevant sources of spermidine, especially:
* mushrooms (trumpet mushrooms)
* mushrooms (particularly trumpet mushrooms)
* [[soy]]  
* [[soy]]  
* pine nuts
* pine nuts
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* legumes  
* legumes  
* nuts  
* nuts  
* seeds<ref name="Zheng2022">https://www.frontiersin.org/articles/10.3389/fnut.2022.843616/full</ref>
* seeds<ref name="Zheng2022">{{Cite journal|title=Serum Spermidine in Relation to Risk of Stroke: A Multilevel Study|date=2022|url=https://www.frontiersin.org/article/10.3389/fnut.2022.843616|journal=Frontiers in Nutrition|volume=9|last=Zheng|first=Liqiang|last2=Xie|first2=Yanxia|last3=Sun|first3=Zhaoqing|last4=Zhang|first4=Rui|last5=Ma|first5=Yanan|last6=Xu|first6=Jiahui|last7=Zheng|first7=Jia|last8=Xu|first8=Qianyi|last9=Li|first9=Zhao|last10=Guo|first10=Xiaofan|last11=Sun|first11=Guozhe|doi=10.3389/fnut.2022.843616/full|issn=2296-861X}}</ref>


==Theory==
==Theory==
A balanced diet can help maintain high levels of spermidine, but spermidine of also sold as a dietary supplement.<ref name="Zheng2022"/>
A balanced diet can help maintain high levels of spermidine, but spermidine of also sold as a dietary supplement.<ref name="Zheng2022" />


==Evidence==
==Evidence==
===Hair loss===
===Hair loss===
Spermidine has been tested for a number of different uses, and there is evidence that it is effective for [[hair loss]] (alopecia),<ref name="Ramot2011">https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022564</ref><ref name="Rinaldi2017">https://doi.org/10.5826/dpc.0704a05</ref> although almost all these studies have been co-authored by and funded by spermidine supplement producers.<ref name="Edzard2020"/>
Spermidine has been tested for a number of different uses, and there is evidence that it is effective for [[hair loss]] (alopecia),<ref name="Ramot2011">{{Cite journal|title=Spermidine Promotes Human Hair Growth and Is a Novel Modulator of Human Epithelial Stem Cell Functions|date=2011-07-27|url=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022564|journal=PLOS ONE|volume=6|issue=7|pages=e22564|last=Ramot|first=Yuval|last2=Tiede|first2=Stephan|last3=Bíró|first3=Tamás|last4=Bakar|first4=Mohd Hilmi Abu|last5=Sugawara|first5=Koji|last6=Philpott|first6=Michael P.|last7=Harrison|first7=Wesley|last8=Pietilä|first8=Marko|last9=Paus|first9=Ralf|language=en|doi=10.1371/journal.pone.0022564|pmc=PMC3144892|pmid=21818338|issn=1932-6203}}</ref><ref name="Rinaldi2017">{{Cite journal|title=A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study|date=2017-10-31|url=https://dpcj.org/index.php/dpc/article/view/dermatol-pract-concept-articleid-dp0704a05|journal=Dermatology Practical & Conceptual|pages=17–21|last=Rinaldi|first=Fabio|last2=Marzani|first2=Barbara|last3=Pinto|first3=Daniela|last4=Ramot|first4=Yuval|language=en|doi=10.5826/dpc.0704a05|pmc=PMC5718121|pmid=29214104|issn=2160-9381}}</ref> although almost all these studies have been co-authored by and funded by spermidine supplement producers.<ref name="Edzard2020" />


===Endothelial function improvements ===
===Endothelial function improvements ===
Matsumoto et al. 2019 conducted a double-blinded placebo-controlled study of a yogurt containing [[Bifidobacterium animalis]] subsp. lactis (Bifal) and the amino acid [[arginine]], concluding that this increased the production of putrescine, a spermidine precursor, which increased spermidine levels, resulting in improved a marker of [[endothelial dysfunction|endothelial function]] in healthy adults after 12 weeks.<ref name="Matsumoto2019"/> The [[Wirth-Scheibenbogen hypothesis]] of ME/CFS states that [[endothelial dysfunction]] is the cause of the symptoms of ME/CFS. Matsumoto's study also suggested that the yogurt is likely to prevent or reduce the risk of [[atherosclerosis]], and found no self-reported changes in mental or physical health, and that the yogurt did not affect weight or vital signs, did not cause safety issues, and did not have a negative effect on blood parameters.<ref name="Matsumoto2019">https://www.mdpi.com/resolver?pii=nu11051188</ref>
Matsumoto et al. 2019 conducted a double-blinded placebo-controlled study of a yogurt containing [[Bifidobacterium animalis]] subsp. lactis (Bifal) and the amino acid [[arginine]], concluding that this increased the production of putrescine, a spermidine precursor, which increased spermidine levels, resulting in improved a marker of [[endothelial dysfunction|endothelial function]] in healthy adults after 12 weeks.<ref name="Matsumoto2019" /> The [[Wirth-Scheibenbogen hypothesis]] of ME/CFS states that [[endothelial dysfunction]] is the cause of the symptoms of ME/CFS. Matsumoto's study also suggested that the yogurt is likely to prevent or reduce the risk of [[atherosclerosis]], and found no self-reported changes in mental or physical health, and that the yogurt did not affect weight or vital signs, did not cause safety issues, and did not have a negative effect on blood parameters.<ref name="Matsumoto2019">{{Cite journal|title=Endothelial Function is improved by Inducing Microbial Polyamine Production in the Gut: A Randomized Placebo-Controlled Trial|date=May 2019|url=https://www.mdpi.com/2072-6643/11/5/1188|journal=Nutrients|volume=11|issue=5|pages=1188|last=Matsumoto|first=Mitsuharu|author-link=|last2=Kitada|first2=Yusuke|author-link2=|last3=Naito|first3=Yuji|author-link3=|last4=|first4=|author-link4=|last5=|first5=|author-link5=|last6=|first6=|author-link6=|last7=|first7=|last8=|first8=|last9=|first9=|language=en|doi=10.3390/nu11051188|pmc=|pmid=|access-date=|issn=2072-6643|quote=|via=}}</ref>
{{See also|Wirth-Scheibenbogen hypothesis}}
{{See also|Wirth-Scheibenbogen hypothesis}}


===Animal experiments===
===Animal experiments===
Experiments on animals (rodents) provide evidence that higher polyamine intake inhibits the emergence of tumors (including cancer) in rodents, promote the growth of existing, and that spermidine has similar effects to [[caloric restriction]] ] including causing increased anticancer immune-surveillance in mice (when spermidine or other polyamines are increased in the diet) - increasing life span and [[autophagy]] in worms, flies, yeast, and mice.<ref name="Schwarz2018">https://www.impactaging.com/full/10/19</ref>
Experiments on animals (rodents) provide evidence that higher polyamine intake inhibits the emergence of tumors (including cancer) in rodents, promote the growth of existing, and that spermidine has similar effects to [[caloric restriction]] - including causing increased anticancer immune-surveillance in mice (when spermidine or other polyamines are increased in the diet) - increasing life span and [[autophagy]] in worms, flies, yeast, and mice.<ref name="Schwarz2018">{{Cite journal|title=Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline|date=2018-01-08|url=https://www.aging-us.com/article/101354/text|journal=Aging|volume=10|issue=1|pages=19–33|last=Schwarz|first=Claudia|last2=Stekovic|first2=Slaven|last3=Wirth|first3=Miranka|last4=Benson|first4=Gloria|last5=Royer|first5=Philipp|last6=Sigrist|first6=Stephan J.|last7=Pieber|first7=Thomas|last8=Dammbrueck|first8=Christopher|last9=Magnes|first9=Christoph|last10=Eisenberg|first10=Tobias|last11=Pendl|first11=Tobias|doi=10.18632/aging.101354|pmid=29315079|issn=1945-4589}}</ref>


===Cognitive dysfunction ===
===Cognitive dysfunction ===
Spermidine has shown promise for improving [[cognitive impairment]] in older adults with cognitive decline and in patients with dementia.<ref name="Pekar2020">https://link.springer.com/article/10.1007/s00508-020-01758-y</ref>
Spermidine has shown promise for improving [[cognitive impairment]] in older adults with cognitive decline and in patients with dementia.<ref name="Schwarz2018" /><ref name="Pekar2020">{{Cite journal|title=The positive effect of spermidine in older adults suffering from dementia|date=2021-05-01|url=https://doi.org/10.1007/s00508-020-01758-y|journal=Wiener klinische Wochenschrift|volume=133|issue=9|pages=484–491|last=Pekar|first=Thomas|last2=Bruckner|first2=Katharina|last3=Pauschenwein-Frantsich|first3=Susanne|last4=Gschaider|first4=Anna|last5=Oppliger|first5=Martina|last6=Willesberger|first6=Julia|last7=Ungersbäck|first7=Petra|last8=Wendzel|first8=Aribert|last9=Kremer|first9=Alexandra|last10=Flak|first10=Walter|last11=Wantke|first11=Felix|language=en|doi=10.1007/s00508-020-01758-y|pmc=PMC8116233|pmid=33211152|issn=1613-7671}}</ref>


There are no clinical trials of spermidine published for [[ME/CFS]], [[fibromyalgia]] or [[Long COVID]] so effectiveness, safety and side effects in these patients are unknown.
There are no clinical trials of spermidine published for [[ME/CFS]], [[fibromyalgia]] or [[Long COVID]] so effectiveness, safety and side effects in these patients are unknown.
Line 37: Line 37:


==Risks and safety==
==Risks and safety==
A very large trial found an increased risk of stroke in healthy people taking spermidine supplement.<ref name="Zheng2022"/>
A very large trial found an increased risk of stroke in healthy people taking spermidine supplement.<ref name="Zheng2022" />


==Costs and availability==
==Costs and availability==

Revision as of 10:38, June 30, 2022

Spermidine or spermidin or C7H19N3 is a natural component of our cells that is found in sperm, different fruits and vegetables, meat, and cheese.[1][2] Spermidine is essential for healthy metabolism in humans.[3] Two-thirds of the spermidine levels in humans are maintained through eating a healthy, balanced diet combined with certain bacteria in the digestive tract, the remaining third of the spermidine is produced by the body's own cells.[4][5]

Spermidine is a polyamine found in almost all tissues in association with nucleic acids and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine.[2]

Sources[edit | edit source]

The main sources of spermidine in humans are plant- and fungal-derived products are the most relevant sources of spermidine, especially:

  • mushrooms (particularly trumpet mushrooms)
  • soy
  • pine nuts
  • wheat germ
  • whole grain products
  • vegetables
  • legumes
  • nuts
  • seeds[3]

Theory[edit | edit source]

A balanced diet can help maintain high levels of spermidine, but spermidine of also sold as a dietary supplement.[3]

Evidence[edit | edit source]

Hair loss[edit | edit source]

Spermidine has been tested for a number of different uses, and there is evidence that it is effective for hair loss (alopecia),[6][7] although almost all these studies have been co-authored by and funded by spermidine supplement producers.[4]

Endothelial function improvements[edit | edit source]

Matsumoto et al. 2019 conducted a double-blinded placebo-controlled study of a yogurt containing Bifidobacterium animalis subsp. lactis (Bifal) and the amino acid arginine, concluding that this increased the production of putrescine, a spermidine precursor, which increased spermidine levels, resulting in improved a marker of endothelial function in healthy adults after 12 weeks.[8] The Wirth-Scheibenbogen hypothesis of ME/CFS states that endothelial dysfunction is the cause of the symptoms of ME/CFS. Matsumoto's study also suggested that the yogurt is likely to prevent or reduce the risk of atherosclerosis, and found no self-reported changes in mental or physical health, and that the yogurt did not affect weight or vital signs, did not cause safety issues, and did not have a negative effect on blood parameters.[8]

Animal experiments[edit | edit source]

Experiments on animals (rodents) provide evidence that higher polyamine intake inhibits the emergence of tumors (including cancer) in rodents, promote the growth of existing, and that spermidine has similar effects to caloric restriction - including causing increased anticancer immune-surveillance in mice (when spermidine or other polyamines are increased in the diet) - increasing life span and autophagy in worms, flies, yeast, and mice.[9]

Cognitive dysfunction[edit | edit source]

Spermidine has shown promise for improving cognitive impairment in older adults with cognitive decline and in patients with dementia.[9][10]

There are no clinical trials of spermidine published for ME/CFS, fibromyalgia or Long COVID so effectiveness, safety and side effects in these patients are unknown.

Clinicians[edit | edit source]

Risks and safety[edit | edit source]

A very large trial found an increased risk of stroke in healthy people taking spermidine supplement.[3]

Costs and availability[edit | edit source]

Spermidine is expensive compared to other nutritional supplements.[citation needed]

Notable studies[edit | edit source]

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. "Spermidine". PubChem. Retrieved June 30, 2022.
  2. 2.0 2.1 "Spermidine". DrugBank. Retrieved June 30, 2022.
  3. 3.0 3.1 3.2 3.3 Zheng, Liqiang; Xie, Yanxia; Sun, Zhaoqing; Zhang, Rui; Ma, Yanan; Xu, Jiahui; Zheng, Jia; Xu, Qianyi; Li, Zhao; Guo, Xiaofan; Sun, Guozhe (2022). "Serum Spermidine in Relation to Risk of Stroke: A Multilevel Study". Frontiers in Nutrition. 9. doi:10.3389/fnut.2022.843616/full. ISSN 2296-861X.
  4. 4.0 4.1 Ernst, Edzard (May 27, 2020). "Spermidine, the new 'wonder supplement'? SADLY NOT!". edzardernst.com. Retrieved June 30, 2022.
  5. Madeo, Frank; Eisenberg, Tobias; Pietrocola, Federico; Kroemer, Guido (January 26, 2018). "Spermidine in health and disease". Science. 359 (6374): eaan2788. doi:10.1126/science.aan2788. ISSN 0036-8075.
  6. Ramot, Yuval; Tiede, Stephan; Bíró, Tamás; Bakar, Mohd Hilmi Abu; Sugawara, Koji; Philpott, Michael P.; Harrison, Wesley; Pietilä, Marko; Paus, Ralf (July 27, 2011). "Spermidine Promotes Human Hair Growth and Is a Novel Modulator of Human Epithelial Stem Cell Functions". PLOS ONE. 6 (7): e22564. doi:10.1371/journal.pone.0022564. ISSN 1932-6203. PMC 3144892. PMID 21818338.
  7. Rinaldi, Fabio; Marzani, Barbara; Pinto, Daniela; Ramot, Yuval (October 31, 2017). "A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study". Dermatology Practical & Conceptual: 17–21. doi:10.5826/dpc.0704a05. ISSN 2160-9381. PMC 5718121. PMID 29214104.
  8. 8.0 8.1 Matsumoto, Mitsuharu; Kitada, Yusuke; Naito, Yuji (May 2019). "Endothelial Function is improved by Inducing Microbial Polyamine Production in the Gut: A Randomized Placebo-Controlled Trial". Nutrients. 11 (5): 1188. doi:10.3390/nu11051188. ISSN 2072-6643.
  9. 9.0 9.1 Schwarz, Claudia; Stekovic, Slaven; Wirth, Miranka; Benson, Gloria; Royer, Philipp; Sigrist, Stephan J.; Pieber, Thomas; Dammbrueck, Christopher; Magnes, Christoph; Eisenberg, Tobias; Pendl, Tobias (January 8, 2018). "Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline". Aging. 10 (1): 19–33. doi:10.18632/aging.101354. ISSN 1945-4589. PMID 29315079.
  10. Pekar, Thomas; Bruckner, Katharina; Pauschenwein-Frantsich, Susanne; Gschaider, Anna; Oppliger, Martina; Willesberger, Julia; Ungersbäck, Petra; Wendzel, Aribert; Kremer, Alexandra; Flak, Walter; Wantke, Felix (May 1, 2021). "The positive effect of spermidine in older adults suffering from dementia". Wiener klinische Wochenschrift. 133 (9): 484–491. doi:10.1007/s00508-020-01758-y. ISSN 1613-7671. PMC 8116233. PMID 33211152.