What Are the Benefits of Spermidine?

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Story at-a-glance -

  • Spermidine, a polyamine compound associated with aging and other metabolic functions, was originally isolated from semen, but is also found in foods like aged cheese, miso and natto
  • Polyamines encourage autophagy, your body’s “self-eating” process for removing cellular debris, which affects aging and longevity
  • Research also has shown polyamines like spermidine can protect you against food allergies, cancer and heart disease
  • Spermidine has been shown to restore the internal body clock of lab mice, suggesting it may be useful for adding years onto your life and acting as a sleep aid

By Dr. Mercola

Despite its somewhat sexualized name, spermidine, which one source1 calls the “most unappetizing-sounding health boon ever,” is a beneficial compound that so happens to have been first isolated in human semen. Well-known food sources of spermidine include aged cheese and fermented soy products, as well as chicken, mushrooms, pears and potatoes.

If you eat any of those foods regularly, you’re likely getting healthy doses of spermidine. Let’s take a closer look at some of the benefits of spermidine, especially as it relates to its involvement with autophagy, the process your body uses to destroy and recycle cellular components.

What Is Spermidine?

While the term spermidine seems to imply a substance originating from sperm, it is actually a polyamine compound with various metabolic functions found in living tissues and foods like aged cheese and fermented soy. It is so named because it was originally isolated from semen. As an organic compound having more than two amino groups, polyamines are essential components of your cells.

Importantly, polyamines encourage cellular autophagy, which has positive implications for aging and longevity, as discussed in the featured video by Naomi Whittel, former CEO of Twinlab and author of "Glow 15: A Science-Based Plan to Lose Weight, Revitalize Your Skin, and Invigorate Your Life."

Autophagy means "self-eating" and refers to the processes by which your body cleans out cellular debris, including toxins, and recycles damaged cell components. Because these processes tend to diminish as you age, it is important you become aware of compounds like spermidine known to boost your body’s antiaging capacity.

Research has shown you also need compounds like spermidine to protect against food allergies, cancer and heart disease. According to a study published in Trends in Food Science & Technology, polyamines such as spermidine, putrescine and spermine play various roles in human cellular metabolism and the synthesis of protein, RNA and DNA.2 The study authors also note:3

“[F]ood is an important source of the polyamines required to support cell renewal and growth. Although the bioavailability and the mechanism of the uptake of polyamines in the gastrointestinal tract are not fully established, it is evident at least some proportion of the polyamines in the diet can be absorbed and utilized by the body.”

Dietary intake of polyamines like spermidine are estimated to be higher in the Mediterranean region (700 micromoles per day) than Northern Europe and the U.K. (350 to 500 micromoles) as well as the U.S. (250 to 550 micromoles).4,5 As to the differences in consumption by region, one study author said, “These dietary differences in the pattern of foods and polyamine intake have been associated with differences in the incidence of chronic diseases — the Mediterranean diet is known to be protective.”6

Higher Spermidine Intake Linked to Lower Mortality

A 2018 study published in The American Journal of Clinical Nutrition7 involving 829 participants ages 45 to 84 linked higher spermidine intake to lower mortality. Diets involving three levels of spermidine consumption were assessed through more than 2,500 dietitian-administered food questionnaires conducted in 1995, 2000, 2005 and 2010.

During the follow-up assessments, which took place between 1995 and 2015, 341 participants had died. About the results, the study authors stated, “The difference in mortality risk between the top and bottom third of spermidine intakes was similar to that associated with a 5.7-year younger age. Our findings lend epidemiologic support to the concept that nutrition rich in spermidine is linked to increased survival in humans.”8

Lower Your Child’s Risk of Food Allergies With Spermidine

A 2009 study conducted at Belgium’s University of Liege,9 uncovered a connection between polyamine intake and the development of food allergies. They assert the concentrations of spermidine and spermine in mother’s breast milk are likely influenced by diet, genetics and lifestyle factors. Their findings suggest:10

  • Spermidine and spermine concentrations are generally lower in infant formulas than in a mother’s breast milk
  • A baby’s probability of developing a food allergy can reach 80 percent if the mean spermine concentration in the milk they are given is lower than 2 micromolar/milliliter (nmol/ml)
  • The baby’s chances of developing a food allergy falls to zero if the mean spermine concentration in their milk is higher than 13 nmol/ml
  • The intestinal permeability to macromolecules in premature babies differs depending on whether they are fed breast milk or infant formula

The study authors11 suggest one goal may be to try to increase the polyamine content in human milk as a possible means of reducing diet-related allergies in childhood. After all, they said, with respect to preliminary studies performed on rats, it is possible to modify the polyamine content in their milk through diet. In fact, amino-acids such as arginine and methionine have been shown to increase spermine concentration in milk, they note.

Spermidine Shown to Aid in Diabetes Management

A 2011 South Korean study12 suggests spermidine plays an important role in the protection of your pancreatic cells, which can be very helpful if you have Type 2 diabetes. The researchers note insulin resistance as a key factor for the disease as well as endoplasmic reticulum (ER) stress. As such, they stated:13

“With an increase in ER stress, pancreatic beta cells start to undergo apoptosis (cell death), leading to a decline in the pancreatic beta cell population. The ER stress arises due to unfolded protein response. Recently, spermidine [has become known] for increasing the longevity in most of the eukaryotes … via induction of the autophagy pathway.

Hence, spermidine can be a candidate for the treatment [of] Type 2 diabetes. Autophagy genes are regulated by mTOR (mammalian target of rapamycin) dependent or independent pathway via AMP-activated protein kinase (AMPK). Hence either inhibition of mTOR or activation of AMPK by spermidine will play two crucial roles: first being the activation of autophagy and second the reduction of ER stress, which will reduce beta cell death by apoptosis.

Thus, [spermidine] can be a novel therapeutic candidate in the treatment of insulin resistance in Type 2 diabetes and the preservation of pancreatic beta cell mass.”

Consume More Spermidine to Boost Your Cardiac Health

The authors of 2016 research published in the journal Nature Medicine,14 which involved adding spermidine to the drinking water of lab mice, suggest the compound has cardioprotective properties and may help extend longevity. With respect to the mice receiving the compound, researchers found spermidine feeding:15

  • Enhanced cardiac autophagy, mitophagy and mitochondrial respiration
  • Improved the mechano-elastic properties of cardiomyocytes, which coincided with increased titin phosphorylation and suppressed subclinical inflammation
  • Preserved diastolic function
  • Reduced cardiac hypertrophy

After purposely raising the mice’s blood pressure to mimic hypertension-induced congestive heart failure, the team noticed spermidine feeding delayed the progression to heart failure by:16

  • Reducing systemic blood pressure
  • Increasing titin phosphorylation
  • Preventing cardiac hypertrophy and a decline in diastolic function

“The mice not only live longer when we supplement spermidine in their drinking water, but they also are healthier in terms of cardiac function,” noted study coauthor Frank Madeo, Ph.D., professor at the Institute of Molecular Biosciences at Austria’s Medical University of Graz.17

Spermidine Shown to Protect Against Liver Damage and Cancer

Research published in the 2017 journal Cancer Research18 demonstrates how spermidine can be used to prevent liver fibrosis and hepatocellular carcinoma (HCC), a common type of liver cancer, in lab mice. After receiving a 3 millimolar (mM) spermidine supplement in their drinking water, researchers noted the mice lived longer.

In addition, the spermidine-treated mice were less likely than their untreated counterparts to develop liver fibrosis and cancerous liver tumors, even if they were predisposed for those conditions. Whereas the mice groups treated lifelong with spermidine achieved a 25 percent greater life extension, those treated at older ages saw only a 10-percent increase in longevity.

"[We saw] a dramatic increase in life span of animal models, as much as 25 percent," said study author Leyuan Liu, Ph.D., assistant professor at the Texas A&M Institute of Biosciences and Technology Center for Translational Cancer Research. "In human terms, that would mean instead of living to about 81 years old, the average American could live to be over 100."19

Although the results seem promising, Liu is quick to note the results are preliminary and the research has yet to move beyond animal models. "It's still early," he said, "but perhaps one day this approach will provide a novel strategy to prolong lifespans, prevent or reverse liver fibrosis and prevent, delay or cure hepatocellular carcinoma in humans."20

Restore Your Internal Body Clock and Achieve Better Sleep With Spermidine

A 2015 study21 conducted by the department of biological chemistry at Weizmann Institute of Science, in Rehovot, Israel, found giving spermidine to lab mice helped reverse age-related impacts on their internal body clocks. Overall, the researchers found increased polyamine levels helped:22

  • Regulate the circadian period in both cultured cells and lab mice
  • Modulated the interaction between core-clock genes Cryptochrome Circadian Regulator 1 (CRY1) and Period Circadian Regulator 2 (PER2)
  • Reversed age-related lengthening of the circadian period in lab mice

The study authors said, “Our findings suggest a crosstalk between circadian clocks and polyamine biosynthesis and open new possibilities for nutritional interventions against the decay in the body clock’s function with age.”23 About the findings, Medical Daily notes, “If these results could be replicated in humans … spermidine could have profound implications as a sleep aid, and even for ‘turning back the clock’ to beat age-related disease.”24

You Need More Spermidine as You Age

While spermidine is beneficial at any age, it becomes even more important as you age. A 2006 study published in the Journal of Biochemistry25 measured changes in polyamine levels during aging by using 2-, 10- and 26-week-old female mice. Notably, the polyamine levels in the brain, pancreas and uterus remained the same for all three age groups.

The amount of spermidine found in the intestine decreased slightly and fell significantly in the heart, kidney, liver, lung, ovary, spleen, stomach and thymus, as well as muscle. In the skin, the level of spermidine was maximal in 10-week-old mice and markedly reduced in the 26-week-old group. The study authors asserted, “The results suggest maintenance of polyamine levels may play important roles in the function of the pancreas, brain and uterus in 3- to 26-week-old mice.”26

In humans, the reality is your cell growth slows dramatically without polyamine synthesis. In fact, as you age, cell growth could actually stop unless you consume foods containing polyamines which, by the way, also have been shown to help hair-loss conditions.27 As you can imagine, if you’re not growing new cells, your tissues and organs will begin to deteriorate, accelerating aging. That is why it is important to obtain sufficient amounts of spermidine and the other polyamines in your daily diet.

Although spermidine and the other polyamines are beneficial for nearly everyone, at least one study suggests you should avoid high intakes if you have cancer. A 2014 study published in World Journal of Gastroenterology28 notes the proliferative characteristics of polyamines with respect to gastric cancer. Although polyamines do not cause cancer, research suggests they could encourage the growth and spreading of existing cancer tumors.29

Foods High in Spermidine

Studies suggest polyamines like spermidine are present in aged (fermented) cheese, including blue cheese, Brie, cheddar, Swiss, Gouda, Gruyere, Manchego and Parmesan. Other foods known for their high spermidine content are:30,31,32

Beef

Chicken

Cooked broccoli and cauliflower

Green peas

Green peppers

Miso

Mushrooms

Natto (fermented soy)

Nuts and seeds, such as almonds, hazelnuts and pistachios

Pears

Pork

Potatoes

Salmon roe

Turkey

Wheat germ

Research performed in 2011 at Sweden’s Karolinska Institute found vegetables and meat products to be among the richest sources of spermidine.33 The scientists noted the content of polyamines in aged cheese, however, which has the highest spermidine content of all dairy products, varied considerably between studies.

As you can see above, there are plenty of foods rich in spermidine from which to choose. Since you cannot afford to miss out on this beneficial antiaging compound that has been shown to possess anticancer and cardioprotective properties, you’ll want to ensure your daily diet includes one or more spermidine-rich foods.