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As we age, our desire to maintain youthful vigor becomes more profound. Spanish explorers famously traveled on a global quest for a literal fountain of youth. But what if the secret to maintaining youthfulness and vitality could be found in our own bodies?
Emerging scientific research suggests that the answer to extending our lifespan may lie in a compound called spermidine. Spermidine is not only found in the human body; many plant and animal food sources are also loaded with this precious longevity compound.
The latest evidence shows that spermidine consumption comes with many health benefits. From promoting cellular rejuvenation to improving cardiovascular health and brain function, spermidine holds great promise in optimizing our well-being. As a result, spermidine has captivated the interest of researchers and youth seekers alike. In this article, we delve deeper into the health benefits of spermidine and analyze the evidence supporting those claims.
First discovered in the 1678s by Antonie van Leeuwenhoek upon self-experimentation. Spermidine is the dominant polyamine with two or more primary amino groups. It is a naturally occurring compound in ribosomes (the site inside a cell where protein synthesis occurs) and other living tissues. In the human body, it is synthesized from its precursor putrescine and used to produce spermine, another important polyamine.
Spermidine, spermine, and other polyamines are primarily responsible for cell growth, division, proliferation, and differentiation. While the mechanism remains unknown, they appear to be required for DNA synthesis, DNA stability, and apoptosis, a method of programmed cell death used to eliminate unwanted cells.
Unfortunately, the levels of polyamines, including spermidine, diminish with aging, according to a 2019 study in the Journal of Autophagy. As a result, it becomes crucial to replenish this loss, either by taking supplements or consuming foods rich in spermidine, such as those listed above.
Cellular rejuvenation, longevity, and anti-aging effects are the primary reason spermidine has recently gained the spotlight in recent years. Spermidine supplements are becoming more popular, and there is an ever-increasing demand for this compound, thanks to our desire for improved health span and lifespan.
Interestingly, scientists have known about polyamines and their role in cellular metabolism for a long time. However, they only recently learned about spermidine levels diminishing as we age — opening up a new frontier of science for enhancing longevity and improving health.
Many animal and human studies suggest that spermidine plays a significant role in delaying aging and age-related diseases. For example, research published in the American Journal Of Clinical Nutrition shows that a diet rich in spermidine significantly improves longevity and reduces the death rate or mortality.
However, the exact mechanism of action of spermidine remains to be understood, with most research so far pointing to the process of
autophagy. For example, the authors of a 2018 research paper note that spermidine extends lifespan by promoting autophagy and might be as powerful as rapamycin — an FDA-approved immunosuppressant with potent autophagy stimulatory properties. However, before we delve into how spermidine promotes autophagy, let's first understand the role of autophagy in longevity.
Autophagy (Latin for self-eating) is a process that occurs when the body cleanses damaged cells by "eating them." Those who practice intermittent fasting may be familiar with this process, which is believed to begin after 16 hours of fasting. Cells use autophagy to degrade their old and damaged parts and reuse them for either cellular repair or generate new cells. In a sense, autophagy is the body recycling old and damaged components and re-utilizing them.
However, research suggests that the rate of autophagy decreases with age, leading to an accumulation of damaged and aged cells. The failure of this recycling process, in turn, has been linked to many age-related conditions, such as neurodegeneration, infections, and numerous autoimmune diseases. In addition, while defects in the autophagy mechanism speed up aging, evidence suggests that the promotion of this process can improve health and promote longevity.
Over the last decade, scientists began to test the hypothesis that lifestyle, diet, and certain supplements may help induce autophagy. These include calorie restriction, exercise, intermittent fasting, a ketogenic diet, medications (rapamycin), green tea, and natural supplements like resveratrol, turmeric, NMN, and spermidine.
As a result, plenty of research now suggests that although spermidine supports longevity in many different ways, the primary mechanism involved is autophagy.
For example, a 2009 study showed that spermidine administration markedly extended the lifespan of yeast, flies, worms, and human immune cells. The researchers found that spermidine inhibited certain enzymes known as acetyltransferases. These enzymes are involved in DNA health. As a result, the gene expression in autophagy increased, reducing cell death and enhancing longevity.
Interestingly, a 2010 study showed that while spermidine enhances autophagy in many species, including yeast, worms, flies, and humans, the inactivation of genes for autophagy abolishes the life-enhancing benefits of spermidine in these species. Similarly, the authors of a 2011 study note that spermidine and resveratrol, while inducing autophagy through different pathways, both converge at modifying and inhibiting the same enzymes, i.e., acetyltransferases. Thus, the two supplements not only support longevity but could complement each other.
In addition, a 2014 study found that the primary enzyme that inhibits autophagy is EP300, and supplementing with spermidine turns off the activity of this enzyme — leading to enhanced longevity. Thus, plenty of research has established a strong relationship between spermidine and autophagy. However, as spermidine becomes more and more mainstream, scientists are now exploring its role in specific age-related health conditions like brain and heart disease.
Improving cardiovascular health is the extension of the same phenomenon. For example, a 2016 study found that spermidine shows cardioprotective effects in mice by promoting autophagy and preserving the heart's function. Cardiovascular health problems have become the leading cause of death worldwide, with ischemic heart disease alone accounting for 16 percent of deaths, according to World Health Organization. As a result, finding ways to manage this plethora of health conditions is the need of the hour. And spermidine supplementation might hold the potential as an alternative therapy.
The authors of a 2017 study on lab mice found that spermidine and spermine upregulate or downregulate many proteins and metabolites involved in immune responses, blood coagulation, lipid metabolism, and glutathione (an antioxidant) metabolism pathways. Likewise, a 2019 study found that spermidine supplementation enhances heart cell viability, decreases cell death, reduces infarction size, and improves heart function in mice with a recent heart attack.
After seeing the cardioprotective benefits of spermidine, researchers began conducting human trials. As a result, in a 2022 study, a team of researchers recruited 377 patients with acute myocardial infarction (AMI) and measured their serum spermidine and oxidative stress (free radical damage due to lack of blood flow) indexes. The researchers found that people with higher spermidine levels in their blood had a better survival probability than those with lower spermidine levels, leading researchers to conclude that spermidine could be a potential biomarker for predicting heart attack outcomes. However, more research is needed to make objective claims.
Besides longevity and heart protection, spermidine also greatly benefits the brain and cognitive function and protects against common age-related brain disorders like Alzheimer's and Parkinson's disease. A large body of evidence suggests that spermidine can prove very helpful for an aging brain, especially when the world population is aging very speedily and dementia is becoming more common. For example, a 2020 lab study indicates that the effect of spermidine and spermine on anti-aging is related to improving autophagy and mitochondrial function.
Likewise, a 2020 study shows spermidine inhibits memory loss in worms with Alzheimer's disease and improves behavioral performance, e.g., locomotor capacity, in worms with Parkinson's disease by mitophagy (a type of autophagy). Additionally, spermidine delays accelerated/premature aging by improving DNA repair. Furthermore, a 2021 research paper has shown a link between higher dietary spermidine intake and reduced risk for cognitive impairment in humans. The researchers found that maintaining mitochondrial and autophagic function by spermidine feeding is essential for enhanced cognition.
However, more human-based clinical trials are needed to establish a robust causal relationship between spermidine and improved brain health.
Inflammation is a natural defense mechanism in the body against foreign invaders such as bacteria, viruses, fungi, parasites, and other triggers. However, sometimes, inflammation gets out of hand, leading to significant morbidity and becoming a menace. However, the good news is spermidine may also hold a potential role in inflammatory disorders such as rheumatoid arthritis and inflammatory bowel disease. For example, a 2012 study published in the Journal of Biomedical Science indicates that spermidine shows anti-inflammatory properties by blocking causes of inflammation (such as the nuclear factor kappa B (NF-κB) and MAP kinases (MAPKs) signaling pathways).
Furthermore, a 2017 lab model shows that spermidine has antioxidant properties and protects against oxidative stress by reducing the intracellular accumulation of reactive oxygen species. Reactive oxygen species are free radicals that damage the body in chronic inflammation, such as in rheumatoid arthritis, ischemic heart disease, and many other lung, kidney, and liver pathologies. Likewise, research published in the Journal of Inflammation Research showed that spermidine suppressed the levels of the pro-inflammatory cytokines IL-6 and IL-1β and increased the levels of the anti-inflammatory factor IL-10 in the serum.
As researchers shed more and more light on spermidine, they find great potential for this compound in many disorders. Recent evidence has found that spermidine might prove helpful in several different types of illnesses, from tumors to muscular pathologies and skin diseases to gut problems. For example, a 2023 study indicates that spermidine interferes explicitly with the tumor cell cycle, inhibiting tumor cell proliferation and suppressing tumor growth.
Furthermore, recent research also shows a connection between spermidine and youthful skin and improved gut health.
Spermidine is generally recognized as safe by the FDA or Federal Drug Association. It has excellent tolerability and no known unfavorable effects. Spermidine is found naturally in our bodies and the food we eat. Thus, our body is well adapted to this compound.
Furthermore, research also found no adverse outcomes related to spermidine consumption.
Spermidine is highly beneficial for the body and the mind alike. As time passes and more research emerges, spermidine will continue to increase in popularity, especially for its apparent longevity benefits.
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By Dr. Eric Madrid, M.D.
