Spermidine: Benefits, side-effects, science and research

Spermidine is quickly becoming a big name on the supplement scene. If taken regularly, the supplement can significantly impact health and lifespan.

We all know that eating well and exercising regularly is key to living as long and as healthy a life as possible. The rise of the longevity supplement market offers new options to complement diet and lifestyle changes. This brings us to spermidine, the suspiciously titled polyamine that was first discovered in semen.

Purported to benefit health, longevity, and even fertility, we take an in-depth look at the polyamine that has begun to dominate the supplement space.

Our Q&A covers common questions like what spermidine is, what it is used for, how you can increase dietary spermidine intake, and finally, what spermidine’s benefits are to health and longevity.

What is spermidine?

Dutch scientist Anton Van Leeuwenhoek initially discovered spermidine in 1678 in a sample of human semen [1].

Soon after, it was found in human sperm. In the human body, spermidine is made from its precursor, putrescine, and another polyamine essential for cellular function called spermine. 

Polyamines can attach to numerous kinds of molecules, making them very valuable. They sustain functions, including apoptosis, cell growth, cell proliferation, and DNA stability.

It also shows that polyamines function similarly to growth factors during cell division. This is why putrescine and spermidine are essential for healthy tissue growth and function.

While not a cure-all, spermidine has undeniable benefits for holistic health. With effects ranging from disease protection to hair health and applications in areas as diverse as coronavirus and fertility, regularly taking spermidine supplements can boost the health and longevity effects of a healthy lifestyle.

Maintaining our spermidine levels as we age by eating foods high in spermidine or taking supplements should be a priority in protecting future longevity.

Where is spermidine found?

Spermidine is found in all eukaryotic cells, where it plays an integral role in cell metabolism. In some bacteria, it is an essential growth factor and it is also a polycation at physiological pH.

While spermidine is available in whole foods, it can also be found in higher concentrations in food-extracted supplements – the most effective way of maintaining high spermidine intake.

What food is highest in spermidine?

You can find spermidine in the following:

  • Vegetables: Consuming your weekly fix of veggies can have additional benefits as spermidine is present in a rich harvest of whole foods (mushrooms, broccoli, cauliflower, fresh green pepper). Most of these are particularly common to the longevity-friendly Mediterranean diet and may explain its unparalleled health benefits.
  • Soybean products: Higher amounts are found in soybean products typical to Japanese food like natto, shitake mushroom, amaranth grain and durian.
  • Cereals: a variety of cereals, in particular wheat germ, contain high amounts of spermidine and are a common source for spermidine-rich food supplements.
  • Various cheeses: Finally, a potential health benefit for those often-criticized but delicious cheeses. Keep in mind, there is reason to believe that the true benefit is generally found in aged cheeses such as cheddar, parmesan, gruyere, etc.
Shitake

What is the mechanism of spermidine?

Spermidine supplements have been lauded for their antiaging benefits, but how does spermidine actually work inside the body?

Common dietary supplements are designed to provide your body with nutrients missing from the modern diet and protect against deficiencies. Longevity supplements like spermidine instead contain active ingredients that work on the molecular pathways that control how we age.

As we age, we accumulate a variety of molecular and cellular damage that results in the hallmarks of aging. Longevity supplements work on the pathways that control the aging process rather than on aging itself.

For example, spermidine induces autophagy, the process of cellular rejuvenation, through the TOR kinase pathway. Autophagy occurs naturally in cells as it regulates cellular metabolism.

Autophagy also balances nutrients during cell stress so can be can be accelerated by fasting or by caloric restriction mimetics (CRMs) like spermidine that mimic fasting’s effects on the body [1].

During autophagy, cells reuse their old or damaged organelles to achieve cellular renewal and its anti-aging benefits. Indeed, autophagy is thought to limit inflammation and oxidative stress, the main culprits involved in aging and related diseases.

Read more about what happens to your body when you take spermidine supplements HERE.

How to increase your spermidine levels in your body?

Unfortunately, our body accumulates damage as we age, increasing our propensity for disease. Likewise, our natural spermidine levels gradually decline with age.

However, this can be rectified by eating foods high in spermidine and taking spermidine-rich natural supplements, thus limiting the impact of aging on longevity.

While it is generally beneficial to enjoy a varied diet rich in whole foods, the most effective way to attenuate declining spermidine levels is by taking longevity supplements.

Although not monitored by the FDA with the same regularity as pharmaceutical drugs, longevity supplements commonly contain ingredients found naturally in the body and food, so they pair high efficacy with low toxicity.

Spermidine supplements are most commonly extracted from wheat germ and are available in powder or tablet form and, when taken regularly, can effectively improve longevity.

A hot topic on the longevity supplement scene, several competing brands of spermidine supplements are all marketed as having anti-aging benefits.

Designed to be taken daily to support a healthy lifestyle, the supplements can also be combined with other longevity ingredients and with longevity diets, such as the Mediterranean diet, for the ultimate effects.

While there are purportedly many options available on channels such as Amazon, be wary of non-food-based synthetic spermidine products with ingredients such as spermidine HCL or “standardized” ingredients, which have unclear safety and efficacy testing.

Longevity Labs’ spermidineLIFE® lays claim to being the first spermidine supplement to hit the global market, including notable scientific advisory board members such as Frank Madeo, the discoverer of the effects of spermidine, and David Sinclair. spermidineLIFE® can be found in drink mix powder or capsule forms.

Other popular food-based options include Oxford Healthspan’s Primeadine.

Read more in our guide to taking longevity supplements.

Safety and side-effects

Since spermidine is a naturally occurring product in the body and part of our natural diet – so is spermidine safe? Yes. The data suggest that spermidine supplementation using a food-extracted spermidine supplement is safe and well-tolerated.

What are the benefits of spermidine supplements?

While not a cure-all, spermidine has undeniable benefits for holistic health. With effects ranging from disease protection to hair health and applications in areas as diverse as coronavirus and fertility, regularly taking spermidine supplements can boost the health and longevity effects of a healthy lifestyle.

What does spermidine do to the body?

Longevity supplements can be used as part of a balanced diet and regular exercise routine to unlock health and longevity.

Increased intake of spermidine may reduce the risk of numerous age-related diseases like cancer, metabolic disease, heart disease, and neurodegeneration [1].

It may also improve cognition and memory. Spermidine can have a neuroprotective effect against neuron damage from inflammation, ischemia, and oxidative stress.

One of the ways it does this is by dissolving amyloid-beta proteins through autophagy. These plaques can build up in the brain and are thought to be related to neurodegenerative diseases like Alzheimer’s.

Indeed, a study showed early signs that spermidine could prevent memory loss in older people suffering from dementia [2].

Taken every day, food-based spermidine supplements could be a promising tool in countering age-related diseases amongst the rapidly growing aging population.

Spermidine may also benefit longevity itself. The supplement mimics the effects of other life-extending interventions like calorie restriction to promote cellular renewal through autophagy.

Spermidine also protects DNA from damage caused by oxidative stress. It has been observed to stabilize mitochondrial DNA, thus protecting against aging caused by mutations in the mitochondrial genome. It may also protect against telomere attrition in mice, the endcaps of chromosomes that shorten with age, directly impacting longevity.

Both genomic instability and telomere shortening are part of the hallmarks of aging, biomarkers used to measure the changes that occur within organisms as they age. Research shows that spermidine can inhibit five of the nine hallmarks of aging.

Read more about the benefits to health and longevity HERE.

Girl on laptop

Unlike traditional dietary supplements that guard against nutrient deficiencies, longevity supplements like spermidine utilize active ingredients to work on the various molecular pathways in the body that affect aging. Aging is defined as a group of damage over time that changes the body.

The external supply of the natural polyamine (meaning it has two or more primary amino groups) spermidine can extend the life span in model organisms, including flies, mice, nematodes, and yeast.

Recent epidemiological evidence suggests that increased spermidine uptake with food reduces overall human cardiovascular and cancer-related mortality [2].

As we get older, our spermidine levels and autophagy rate decline – leaving cells more exposed to damage from the hallmarks of aging. Sustaining our levels as we age by taking supplements or eating high-spermidine foods should be a priority in protecting future longevity.

Spermidine may also help reduce the physical aspects of aging. One of the earliest signs can be seen in our faces (deep wrinkles, fine lines, and sagging skin), which are seemingly inevitable parts of the aging process, and the common fear of looking older has fuelled the skincare and antiaging industries. 

Based on age-old anti aging wisdom from Japanese medical scrolls, supplements combine the active ingredients of spermidine and wheatgerm to:

  • Minimize deep wrinkles
  • Stimulate hair growth and longer lashes
  • Make nails stronger

All contributing to a more youthful appearance.

One study showed spermidine’s antiaging benefits on the skin. It established that its secretions from the Streptococcus bacteria that live in the skin biome promote the formation of elastin, collagen, and lipids in older skin cells, which improves skin barrier function and structure [3].

Read our article about the aesthetic aspects of aging HERE.

Improved reproductive fertility

Spermidine has additionally been associated with improved reproductive fertility in both sexes. With the growing global population, rising cost of living, and pressures of professional life, many people are deciding to delay having children.

If they do choose to become parents, they may encounter some unexpected problems on the way to expecting a baby.

Menopause, when women lose the ability to have children, can occur from age 45, and ovaries can age up to five times faster than any other organ in the body.

While there are several reproductive assistance methods available, research has turned to spermidine.

Over time, ovaries accumulate reactive oxygen species (ROS), a form of oxidative stress that can damage eggs (oocytes) and cause cellular senescence – contributing towards menopause [4].

ROS can cause the female germline stem cells (FGSCs) in the ovaries to develop abnormally. This prevents them from producing viable oocytes, dramatically limiting fertility.

One study hypothesized that spermidine could reduce oxidative stress in FGSCs. The results proved that autophagy and stem cell production were boosted in FGSCs treated with spermidine, therefore reducing oxidative damage [5].

This gives rise to the potential use of the supplement in female fertility therapies. Equally, while men do not undergo the same sharp decline in fertility as in menopause, spermidine may also have potential benefits to male fertility.

As its name suggests, spermidine was first discovered in semen and is important in generating sperm in sexual production. Indeed, infertile men have been found to have lower spermidine levels compared to fertile men [6].

A large part of sexual reproduction is controlled by hormones. One study investigated the effect of the supplement on different hormone levels in men.

It found that taking the supplement for 30 days significantly reduced levels of the stress hormone cortisol, which can majorly impair fertility as a survival mechanism.

It also reduced levels of oestradiol, a type of estrogen linked to reduced sexual function in men. However, levels of testosterone and the sex steroid hormone DHEAS were seen to increase, indicating improved sexual function [7].

Read more about spermidine and improved reproductive fertility HERE.

Spermidine and COVID-1

A regular in medical-related news over the past couple of years has been the continuing COVID-19 pandemic, which has had significant implications for global health, longevity and well-being.

As governments scrambled to control coronavirus, research turned to investigating potential therapeutics to treat its symptoms. Indeed, several studies have investigated the impact of spermidine on immune health.

Using supplements to enhance immune function and reduce inflammation became popular during the pandemic as people took autonomy over their own health. Supplements may help prevent and reduce symptoms of respiratory illnesses like the cold and flu.

The hope was that this could be transferrable to COVID-19 infection. Considering that a major mechanism affected by spermidine is autophagy, which is part of the immune system clearing away pathogens and regulating inflammation, this hypothesis is not so far-fetched.

The advent of the COVID-19 vaccination and its boosters has provided most people with protection against serious coronavirus.

In older people, vaccines are usually less effective as the immune system weakens with age, known as immunosenescence.

This has been evident throughout the pandemic, with those most affected by serious coronavirus generally being older, as well as those with underlying health conditions.

To help prevent this, studies have focused on increasing vaccine efficacy and immune function in older people. One preliminary study investigated whether spermidine supplements increased vaccine efficacy in older subjects [8].

Spermidine was observed to reduce with age in human T cells that are involved in the immune response.

Using supplements restored T cell functioning and autophagy levels, raising hopes of using autophagy-boosting compounds like spermidine to improve vaccine efficiency in older adults.

While there are several pharmacological treatments for those with severe cases of coronavirus, a cure for COVID-19 does not yet exist, and vaccines unfortunately do not offer 100% protection.

There remains a need for novel, effective therapeutics. Promising results from one study found that during infection, the SARS-CoV2 virus reduced spermidine levels as well as cellular autophagy by interfering with metabolic pathways.

Administering spermidine to target these pathways was found to restore autophagy and reduce viral replication. This shows potential for using an autophagy-inducing compound as a treatment for coronavirus [9].

Read more about spermidine and COVID-19 HERE.

Intrigued by spermidine? Find out more in our Supplements Report, and check out our supplements company profiles here.

In closing

Spermidine is a fascinating compound with promising health benefits rooted in robust scientific research. Its potential to support cellular rejuvenation, longevity, cardiovascular health, and cognitive function highlights its relevance in health and wellness.

However, it’s crucial to be aware of potential side effects and consult with healthcare professionals before integrating spermidine into one’s lifestyle.

As ongoing research unveils its mechanisms and applications, individuals can explore spermidine-rich foods and supplements cautiously. Ultimately, spermidine presents an exciting avenue for those seeking to optimize their well-being, but informed decisions and responsible use remain paramount in realizing its potential.

References:

[1] https://clinical-and-molecular-endocrinology.imedpub.com/the-other-legacy-of-antonie-van-leeuwenhoek-the-polyamines.php?aid=19400
[2] https://link.springer.com/article/10.1007/s00508-020-01758-y
[3] https://www.nature.com/articles/s42003-020-01619-4
[4] https://pubmed.ncbi.nlm.nih.gov/31827090/
[5] https://pubmed.ncbi.nlm.nih.gov/31319247/
[6] https://rb.gy/hdevg2
[7] https://rb.gy/wyvmdk
[8] https://elifesciences.org/articles/57950
[9] https://rb.gy/gvwsrv

Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.

The information included in this article is for informational purposes only. The purpose of this webpage is to promote broad consumer understanding and knowledge of various health topics. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.