What is spermidine?
Spermidine is a polyamine, which means it has two or more primary amino groups. It is naturally occurring and widely present in ribosomes and living tissues. It plays a vital role in cell function and survival.
Spermidine was first discovered in 1678 by Dutch scientist Anton Van Leeuwenhoek in human semen samples. Soon after, spermidine was discovered in human sperm. In the body, spermidine is produced from its precursor putrescine. It is a precursor to another polyamine called spermine, which is also important for cell function.
Spermidine and putrescine are known to stimulate autophagy. A system that breaks down intracellular waste products and recycles cellular components. It is an important quality control mechanism for mitochondria, the powerhouse of the cell. Autophagy breaks down and processes damaged or defective mitochondria. Mitochondrial processing is more tightly controlled than previously thought.
Polyamines can bind to many different types of molecules, making them very useful. They support processes such as cell growth, DNA stability, cell proliferation, and apoptosis. Polyamines appear to function similarly to growth factors during cell division. This is why putrescine and spermidine are important for healthy tissue growth and function.
Which foods are high in spermidine?
Grapefruit is a source of spermidine. There are many dietary sources of spermidine, including grapefruit, soy products, legumes, corn, whole grains, chickpeas, peas, green peppers, broccoli, oranges, green tea, rice bran and fresh green peppers.
It is also found in shiitake mushrooms, amaranth seeds, wheat germ, cauliflower, broccoli, and various ripe cheeses and durians.
It’s worth noting that most Mediterranean diets contain spermidine-rich foods. This could at least explain the phenomenon of "blue zones" and why people there tend to live longer than those elsewhere.
You can also take it as a spermidine supplement if you have trouble getting enough from your diet. The synthetic spermidine used in the supplement is the same naturally occurring molecule.
What is putrescine?
Before we delve into some of the interesting research behind spermidine and why some researchers believe it may help slow aging, we should first look at how it is produced.
There are two pathways for putrescine production, although both start with the amino acid arginine.
The first pathway is the conversion of arginine to agmatine with the support of arginine decarboxylase. In the next step, agmatine is converted to N-carbamoylputrescine by agmatine iminohydroxylase. Finally, N-carbamate putrescine is converted into putrescine, and the conversion is completed.
The second pathway simply converts arginine to ornithine, which is then converted to putrescine via ornithine decarboxylase.
What are the uses of spermidine?
Some studies suggest it may prevent liver fibrosis and hepatocellular carcinoma (a common cause of liver cancer). Some people take it as a supplement, believing it may affect aging and extend life.
It is known for its ability to promote autophagy, a cellular recycling program that helps cells remove waste and unwanted components, which is the most likely reason why it may affect aging.
Supplementing or consuming enough spermidine in your diet has some potential health benefits. Even better, it may also influence aging and support health and longevity.
Spermidine and autophagy
As mentioned previously, putrescine can produce spermidine during the process of decarboxylating S-adenosylmethionine from putrescine.
It plays an important role in regulating various biological processes, including maintenance of intracellular pH levels and cell membrane potential. Spermidine also plays a central role in many important biological processes, including aspartate receptors, cGMP/PKG pathway activation, nitric oxide synthase, and cerebral cortical synaptosome activity.
Spermidine is of interest to scientists in the context of aging because it is a key morphogenetic determinant of the lifespan of cells and living tissues.
Spermidine's ability to trigger autophagy is thought to be its primary mechanism by which it delays aging and extends lifespan.
It has been shown to induce autophagy in mouse hepatocytes, worms, yeast, and fruit flies.
Defects in the autophagy machinery and spermidine deficiency are highly associated with shortened lifespan, chronic stress, and acute inflammation.
Anti-inflammatory properties of spermidine
Although the primary way spermidine appears to support longevity is through autophagy, there is also evidence that it supports health and longevity in other ways. Some studies suggest that it has anti-inflammatory properties and is involved in lipid metabolism, cell growth and proliferation, and programmed cell death, known as apoptosis.
It is generally accepted that while inflammation plays a beneficial role in wound healing and fighting off invading pathogens, the persistent inflammation associated with aging (commonly referred to as hyperinflammation) is harmful. Chronic inflammation can hinder the regeneration of healthy tissue, cause immune cell dysfunction, and even accelerate the aging of healthy cells. Spermidine appears to reduce this chronic inflammation and may be a way to slow cell and tissue aging.
Spermidine may slow down aging
In terms of longevity, many animal studies have shown that the use of spermidine can extend lifespan and prevent liver fibrosis and hepatocellular carcinoma. This also appears to be the case with polyamine-rich diets. There is also some evidence that it improves resistance to stress, and age-related declines in spermidine support the onset of age-related diseases.
Lipid metabolism is a known regulator of lifespan, and dysfunctional lipid metabolism can have serious consequences for health and lifespan. Spermidine's role in adipogenesis, the process by which stem cells produce adipocytes (fat cells), and its ability to alter lipid distribution may suggest another way in which spermidine affects lifespan. As part of the adipogenesis process, spermidine promotes the differentiation of preadipocytes into mature adipocytes.
One study showed that administration of alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, completely blocked lipogenesis. Although DFMO remained, administration of spermidine reversed the complete disruption of lipid metabolism. The researchers observed that spermidine also restored the expression of transcription factors required for preadipocyte differentiation and those associated with markers of advanced adipocytes.
If these compounds are combined together, the combination of effective autophagy, reduced inflammation, reduced levels of cellular oxidative stress, improved cell growth, and improved lipid metabolism may contribute to a healthy and long life.
Spermidine may reduce cognitive decline
Research published in 2021 in the journal Cell Reports details dietary spermidine improving cognition and mitochondrial function in flies and mice, complementing some prospective human data. While this study is interesting, it has some limitations and additional dose-response data are needed before firm conclusions can be drawn about cognitive benefits in humans.
Spermidine for cancer and cardiovascular health
There is also some evidence that it may reduce the risk of cardiovascular disease. A 2016 study found that spermidine can reverse the aging clock and improve cardiovascular function in older mice. At the organ level, aged mice given spermidine showed improvements in heart structure and function. Metabolism in these mice also improved due to restoration of mitochondrial structure and function following spermidine supplementation.
In humans, there are two population-based studies (summarized in the same paper) with data showing that spermidine intake is associated with reduced all-cause mortality, cardiovascular mortality, and cancer-related mortality in humans .
Based on these data and other studies, some researchers have concluded that spermidine may slow aging in humans. We should be cautious at this stage as it is still early days for spermidine, but the data so far certainly warrant further study to see if this anti-aging effect can be confirmed.
Observational studies in humans have also found an association between dietary spermidine intake and reduced risk of colon cancer.
Is spermidine safe?
Yes, it is a naturally occurring product in the body and is a natural part of our diet. Data suggest that supplementation with spermidine is safe and well tolerated.
Spermidine side effects
There are no known adverse side effects of spermidine supplementation. Several studies have been conducted on it and the results show that it is well tolerated. Of course, as with any supplement, if you do experience side effects, stop taking it immediately and consult your doctor.