Spermidine 3 mg/capsule

300 mg Wheat Germ Extract with high spermidine content

60 capsules

Ingredients: Separating agent: microcrystalline cellulose, Maltodextrin Vegan capsule – Coating agent: Hydroxypropylmethylcellulose

Content per capsule: (2 x 1 capsule = maximum daily dose) Wheat germ extract 300 mg

Net weight: 29 g Content: 60 vegan capsules Purely plant-based: We use vegetarian capsule shells. The capsule shell is white; we use natural white pigment: calcium carbonate. Free of lactose, nuts, and caffeine. 100% non-GMO product.

Made in China. The quality of the product is ensured by testing institutions accredited in Austria.

Dietary supplement Wheat germ extract* with high spermidine content in capsules. • Wheat germ extract with high spermidine content is obtained through predominantly polyamine-targeted solid-liquid extraction from non-fermented, non-germinated wheat germs (Triticum aestivum). Source: IMPLEMENTING REGULATION (EU) 2020/443 OF THE EUROPEAN COMMISSION dated March 25, 2020

Recommended intake: Take two capsules per day with 200 ml of liquid during a meal. The recommended maximum amount is six milligrams per day.

Storage information: Store below 25°C, dry, and protected from light. Keep the container tightly closed after use.

Minimum durability until end/lot number: see bottom

Important notes: Not suitable for persons under 18 years, pregnant, and breastfeeding women. The recommended daily dose should not be exceeded. Dietary supplements are not a substitute for a varied and balanced diet, which is important together with a healthy lifestyle. Keep out of reach of small children.

Spermidine side effects are not known so far – as long as the recommended maximum amount of six milligrams per day is not exceeded.

 

What is spermidine and what is it used for?

Spermidine, a polyamine, is a natural substance synthesized in living organisms, including bacteria, plants, animals, and humans.

Bioactivities of spermidine contributing to a healthy and long life: Spermidine plays a fundamental role: • in cell growth (cell proliferation and cell differentiation), especially in the regulation of gene expression • in protein synthesis in transcription and translation processes, but also • in inducing autophagy and • in resistance to oxidative cell stress, nitrosative stress, and toxic stress with an overactive HPA axis.

 

  • DNA methylation by spermidine Spermidine

is an epigenetically effective key molecule and, together with S-adenosylmethionine (SAM, Ademetionine; AdoMet), ensures the maintenance of health and the integrity of mitochondria. The methylation status of genes is closely related to age-related changes, and spermidine metabolism is closely linked to the regulation of gene methylation. Age-related changes, including spermidine deficiency, in an altered DNA methylation status, namely increased demethylation in some areas and hypermethylation in other areas of DNA, are considered one of the most important mechanisms underlying age-related pathologies (aging).

 

  • Spermidine protects against the negative consequences of aging and extends lifespan

The age-related increase in abnormal DNA methylation and the resulting pathological changes can be inhibited by timely and sufficient intake of spermidine, thereby extending lifespan.

 

  • Spermidine has the ability to stimulate the process of autophagy

One of the most important effects of spermidine on cell health is its ability to stimulate the process of autophagy, a cellular disposal and recycling system. Autophagy is a cellular process in which damaged or outdated cell components are broken down and removed, but also recycled by saving amino acids for protein synthesis and providing energy under starvation conditions or repairing damage under stress conditions to maintain cell and mitochondrial health. Adequate autophagy is crucial for protecting cells from aging, inflammation, and various diseases.

In 2019, a research group led by Frank Madeo at the Institute of Molecular Biosciences at the University of Graz highlighted the importance of autophagy-mediated bioactivity of spermidine for lifespan extension. Specifically, spermidine induces autophagy by inhibiting the acetyltransferase EP300.

Source: Eisenberg T, Knauer H, Madeo F et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009 Nov;11(11):1305-14.

 

  • Proteasome and Spermidine Interaction:

Proteins are the molecular building blocks and machinery of the cell. Whether serving as structural elements or catalyzing chemical reactions, proteins are involved in nearly all biological processes. They are primarily produced in specialized protein factories called ribosomes in the cell plasma. Additionally, the cell’s powerhouses, mitochondria, have their own protein production sites.

Proteasomes, along with lysosomes, serve as sites for intracellular quality control and the breakdown of no longer needed proteins. Proteasomes degrade these proteins with the consumption of ATP. To do this, substrates must be marked by attaching polyubiquitin chains (ubiquitin system). Proteasomes are responsible for ATP-dependent degradation of: • Misfolded proteins • Non-functional or aged proteins • Proteins with a short half-life • Viral proteins

Proteolysis prevents these proteins from accumulating in cells, and the contained amino acids can be reused.

Proteasome and Spermidine Interaction:

  1. Inhibition of Protein Ubiquitination: Spermidine, a natural polyamine, disrupts protein ubiquitination at high concentrations, influencing growth mechanisms. This includes inhibitory effects on the proteasome endopeptidase complex.
  2. Proteasomal Breakdown: Studies show that the proteasomal breakdown of proteins, such as Spermidine/Spermine N1-acetyltransferase, involves specific amino acid residues, highlighting the complex role of the proteasome in cellular processes.
  3. Autophagy Stimulation: Spermidine acts as a potent trigger for autophagy, a cytoprotective process. It helps maintain cell structure and function, indicating a connection between Spermidine, autophagy, and proteasomal signaling pathways.
  4. Polyamine Inhibition: Polyamine analogs, including Spermidine, inhibit the ubiquitination of specific proteins, preventing their targeted delivery to the proteasome for degradation.

In summary, the interaction between Spermidine and the proteasome involves the modulation of ubiquitination, proteasomal breakdown, and the stimulation of autophagy, contributing to cellular homeostasis and protein quality control.

 

  • Spermidine extends lifespan as it is a caloric restriction mimetic

Our body and cells are constantly supplied with food and thus energy, leading to cell growth, which is further amplified by insulin and insulin-like growth factor IGF-1 and mTOR. For our cells, this means that they continuously age. On the other hand, if we refrain from eating for a while, insulin and IGF-1 levels decrease, and mTOR comes to rest. Cells initiate a “self-cleaning program,” known as autophagy.

The strategic project of VASCage – Research Centre on Vascular Ageing and Stroke – Medical University – Innsbruck, which successfully transitioned to the K1 center VASCage, makes it possible to investigate the effect of spermidine on human lifespan:

In the Bruneck study, the dietary habits of participants were qualitatively and quantitatively recorded over 20 years. The main sources of spermidine in the diet were whole grain products, apples and pears, lettuce, vegetable sprouts, and potatoes. Indeed, the amount of spermidine in the diet of the Bruneck participants was inversely associated with the risk of death, i.e., individuals who consumed a lot of spermidine in their diet had a lower mortality risk over the 20-year follow-up period. Since the decline in autophagic function plays an important role in almost all age-related diseases, it was not surprising that positive effects of spermidine were found in the analysis of deaths due to vascular diseases, tumors, and other diseases. A spermidin-rich diet and spermidin supplementation correlate with increased survival in humans. Individuals who consume a lot of spermidin, at least 80 µmol of spermidin per day, have a significantly lower risk of premature death.

According to this study, the difference in the risk of mortality for individuals whose spermidin intake was in the upper third and those whose intake was in the lower third (<60 µmol per day) is 5.7 years of lifespan.

Sources:

Stefan Kiechl, et al. Higher spermidine intake is linked to lower mortality: a prospective population-based study, The American Journal of Clinical Nutrition, Volume 108, Issue 2, August 2018, Pages 371–380,

Soda, K., Spermine and Spermidine Induce Autophagosome Accumulation and Lysosomal Degradation of β-Amyloid in Human Alzheimer’s Disease Fibroblasts. Society for Experimental Biology and Medicine, 2013, 238 (5), 524– 533.

 

In summary, this data illustrates the vital importance of autophagy in preserving health and extending lifespan, thus preventing diseases associated with aging.

 

Based on these findings, spermidine is a potential caloric restriction mimetic for the prevention and support of various diseases

Due to its beneficial effects on cell growth, protein synthesis, autophagy, and resistance to cell stress, spermidine is considered a natural bioactive compound that can contribute to maintaining health and well-being. Spermidine is a valuable support for a healthy lifestyle and for maintaining health into old age, as well as for preventing premature aging and aging-related diseases. VASCage researchers are investigating how spermidine is absorbed in the human body and the benefits of spermidine supplementation. Spermidine is supplied in the form of spermidine-rich wheat germ extract in capsules. The source of the spermidine is the wheat germ extract from the grain of Triticum aestivum. The wheat germ extract is obtained predominantly by polyamine-targeted solid-liquid extraction from non-fermented, non-germinated wheat germs. The naturally high spermidine content is made available in the form of a highly concentrated extract. The daily intake of spermidine, which can be consumed with a small amount of liquid, should be between three and six milligrams. The vegan capsules are easy to swallow and dissolve quickly.

References: Hinz, M., Arhilger, L., Pigisch, S. et al. Mice lacking the rapamycin target Raptor in gastric pit cells are resistant to gastric damage. Life Sci Alliance 4, e202101075 (2021).”

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  • Spermidine has a role in cell reprogramming and autophagy regulation

Recent findings have attributed functions to spermidine in cell reprogramming and autophagy regulation. Reprogramming enables the nucleus of any cell in the body to revert to an early embryonic developmental stage.

 

  • Spermidine can reduce oxidative damage in cells and enhance protection against oxidative cell damage

Oxidative stress is an imbalance between pro-oxidative and anti-oxidative processes in the body and can lead to cell damage and inflammation.

 

  • Spermidine increases the antioxidant effect of antioxidants

Spermidine suppresses oxidative cell stress (ROS burden), protecting mitochondria and, consequently, all body cells and organs. A spermidine transporter controls spermidine concentration during oxidative stress and mediates the induction of antioxidant proteins. Spermidine can enhance the antioxidant effect of antioxidants when administered before, after, or together with spermidine (Frank Madeo).

 

  • Spermidine has anti-inflammatory effects

Chronic low increases in proinflammatory cytokines and chemokines and the resulting increase in inflammatory biomarkers are associated with age-related functional impairments and increased risks of morbidity and mortality. Spermidine acts as an anti-inflammatory agent in acute and chronic inflammation, attributable to its antioxidant and lysosomal stabilization properties.

 

  • Spermidine improves immune function

Regulatory T cells, or Treg cells, are a specialized subset of T lymphocytes, mostly CD4+ T cells, that regulate the immune system’s self-tolerance. Spermidine obtained through diet promotes the differentiation of naive CD4-positive immune cells, leading to increased anti-inflammatory Treg cells. Simultaneously, there is a reduction in TH17 cells, a cell type significantly involved in inflammatory reactions.

 

  • Spermidine promotes mitochondrial health

Spermidine contributes to the health of mitochondria, known as the powerhouses of cells responsible for producing ATP. Spermidine can help maintain optimal mitochondrial energy levels and protect the function of cell organelles from oxidative attack (ROS) as a whole, contributing to better cell and organ health.

 

  • Spermidine protects brain cells

Maintaining mitochondrial and autophagic function is essential for improved cognition with spermidine supplementation. Spermidine has a positive effect on older adults with dementia, protecting brain cells and the memory apparatus from oxidative cell stress, nitrosative stress, and toxic neuronal stress with an overactive HPA axis (persistent cortisol elevation). Spermidine is involved in synaptic transmission and synaptic plasticity, which underlie learning and memory. The age-related decline in memory can be halted by administering the natural substance spermidine.

Sources:

Miranka Wirth. Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)—study protocol for a randomized controlled trial.

Wirth M, Benson G, Schwarz C, Köbe T, Grittner U, Schmitz D, et al. The effect of spermidine on memory performance in older adults at risk for dementia: a randomized controlled trial. Cortex. 2018;109: 181–8.

Pekar, T., Bruckner, K., Pauschenwein-Frantsich, S. et al. The positive effect of spermidine in older adults suffering from dementia. Wien Klin Wochenschr 133, 484–491 (2021).

The results of a study by Thomas Pekar showed a clear correlation between spermidine intake and the improvement of cognitive performance in individuals with mild and moderate dementia in the group treated with higher spermidine doses. The most significant improvement in test performance was observed in the group of subjects with mild dementia. In comparison, the group with lower spermidine intake showed consistent or declining cognitive performance.

 

  • Spermidine as an important contribution to cell health as a “growth factor.”

The cell is the atom of biology (Paul Nurse). The cell is the simplest structure of which we are certain that it is alive. Proteins are the most important substances in cells. They enable their structure and operation and are thus the actual molecules of life.

 

  • Spermidine and cell growth.

Spermidine is present in all living organisms and in all body cells and is closely related to cell growth. The exact physiological function of spermidine is in growing cells, such as in the production of nucleic acids and proteins or membrane stabilization. Polyamines alter chromatin structure and gene regulation because, due to their positive charge, they bind as cations to DNA and stimulate the deacetylation of histone proteins. The amount of spermidine in the body increases with an acceleration of metabolism. With a slowing of metabolism, spermidine production decreases. The concentration of endogenous spermidine also decreases with aging. Natural circumstances that increase spermidine levels are growth, pregnancy, repair of muscle cells after intense physical exertion, and regeneration of erythrocytes after blood loss and anemia.

Sources:

Kazuei Igarashi, Keiko Kashiwagi: Modulation of cellular function by polyamines. In: The International Journal of Biochemistry & Cell Biology. Volume 42, 2010, p. 39.

Mandal, A. Mandal, H. E. Johansson, A. V. Orjalo, M. H. 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. Volume 110, 2013, p. 2169.

 

  • Spermidine increases overall protein synthesis by 1.5 to 2.0 times

Spermidine is an important factor in promoting protein synthesis. Spermidine increases the ability to synthesize RNA and has a regulatory role at the level of genome transcription and stabilizes proteins at the translation level. Proteins are produced by high-molecular protein factories, the ribosomes. The biosynthetic performance of the ribosomes inside the cells consists of the chemical linkage, the formation of peptide bonds, of twenty different amino acid building blocks into a linear polypeptide chain, typically consisting of several hundred amino acids. So that a protein can develop its biological activity, the amino acid chain must first be “folded” into a three-dimensional structure. Folding represents the maturation of the protein and is a fascinatingly complex process that has occupied generations of researchers. It is based on interactions between the amino acids of a polypeptide chain that form within seconds to minutes.

The growing polypeptide chain is continuously channeled from the site of its origin inside the ribosome through a narrow tunnel to the surface of this molecular machine. Here the folding of the protein begins. This is a complex process that is highly susceptible to errors and can lead to the formation of “misfolded” proteins that are not functional and sometimes even toxic to cells, which can be removed by the process of autophagy. Protein folding disorders are the cause of a variety of diseases and are associated with aging. To counteract these problems, cells have an arsenal of molecular chaperones that make up about ten percent of the cell’s total proteins. Chaperones bind and protect newly synthesized proteins until they have acquired their native three-dimensional structure. They thus prevent unwanted protein aggregations and the formation of “misfolded” proteins.

Spermidine has a binding capacity to DNA, RNA, and various protein molecules and is involved in various cellular functions such as transcription, RNA modification, protein synthesis, and modulation of enzyme activities. It is estimated that a high percentage of polyamines are bound to nucleic acids, proteins, and other negatively charged molecules in the cell through ionic interactions. In summary, spermidine contributes to protein synthesis by promoting the binding of mRNA to ribosomes and also stimulates the process of autophagy, which can contribute to the release of amino acids needed for protein synthesis.

 

  • Contribution to Heart Health

Spermidine has a cardioprotective effect, stabilizing mitochondrial function, exhibiting anti-inflammatory properties, preventing the aging of stem cells, and thus reducing cardiovascular mortality. Supplementing spermidine induces autophagy and prevents the progression of heart aging.

 

  • Contribution to Healthy Sleep

Spermidine also influences sleep behavior. Individuals who do not consume an adequate amount of spermidine have an extended circadian rhythm. Spermidine supplementation can improve sleep architecture.

 

  • Regeneration of Cartilage and Intervertebral Discs

Spermidine shows a protective and regenerative effect on joint cartilage and intervertebral discs. Spermidine improves dysregulated autophagy and spermidine synthesis in aged and osteoarthritic cartilage cells.

 

  • Beauty for Skin and Hair

Spermidine improves the appearance and functional properties of the skin, hair, and nails. Spermidine promotes growth and regeneration of skin-hair-nail tissues by stimulating skin cells and appendage cells and counteracting skin aging. Spermidine exhibits high cell activation in normal human skin fibroblasts (anti-aging effect). Spermidine has anti-inflammatory effects in acute and chronic inflammation, which is attributable to its antioxidant and lysosomal stabilization properties, benefiting the health of skin, hair, and nails.

 

  • Spermidine Lowers Insulin Levels and Reduces the Risk of Diabetes and Obesity

Spermidine is involved in the translation of insulin mRNAs. This insulin-sensitizing property of spermidine opens up the possibility of delaying or preventing insulin-dependent diabetes. There is evidence that spermidine can lower insulin levels. Insulin is a hormone produced by the pancreas that regulates blood sugar levels. High insulin levels are associated with an increased risk of various diseases such as diabetes and obesity. Several studies in animals and human cells have shown that spermidine has a positive impact on insulin levels. A study in mice found that administering spermidine reduced insulin resistance and improved glucose metabolism. Another study found that spermidine can lower insulin levels in human cells by improving insulin secretion and sensitivity.

Source: Oka T, Ohtani M, Suzuki J. Identification of novel molecules regulating differentiation and hormone secretion and clarification of their functional mechanisms in pancreatic endocrine cells. Yakugaku Zasshi. 2010 Mar;130(3):377-88. Japanese. doi: 10.1248/yakushi.130.377. PMID: 20190522.

 

Note: This information is provided for educational purposes and does not substitute for professional medical advice. Always consult with healthcare providers for personalized guidance on health-related matters.

Copyright © Eduard Rappold 2024