While its name may raise a few eyebrows, the natural polyamine – spermidine has remarkable benefits to health and longevity.

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 is spermidine, what is it used for, how can you increase your spermidine levels, and finally, what are spermidine’s benefits to health and longevity?

What is spermidine?

Spermidine is a polyamine found naturally in cells and certain whole foods. It is also available in supplement form. Predicted to be the longevity supplement of 2022 by lifespan expert Dr David Sinclair, spermidine is fast becoming a big name on the supplement scene. Taken regularly, the supplement can have a significant impact on health and lifespan. By mimicking the effects that caloric restriction has on cells in the body, it induces autophagy, the process of cellular renewal thought to have antiaging benefits. As we age, our spermidine levels as well as our rate of autophagy decline, leaving cells more exposed to damage from the hallmarks of aging. 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 taken in supplement form – the most effective way of maintaining your spermidine levels.

What foods are high in spermidine?

• Vegetables – Getting your five-a-day can have additional benefits as spermidine is found in a rich harvest of whole foods from fresh green pepper, cauliflower, broccoli and mushrooms. Some of these ingredients are particularly common to the longevity-friendly Mediterranean diet and may go some way to explaining its unparalleled health benefits.
• A variety of cheeses
• Wheatgerm – Spermidine is also available in high concentrations in the health food wheat germ, a common ingredient in nutritional and longevity supplements.
• Soybean products – Even higher amounts are found in soybean products common to the Japanese diet like natto, shitake mushroom, amaranth grain and durian.  

The science behind 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 antiaging 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 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 pair high efficacy with low toxicity. Spermidine supplements are available in powder or tablet form and when taken regularly can effectively improve longevity. A hot topic on the longevity supplement scene, there are several competing brands of spermidine supplements that are all marketed as having antiaging benefits. Designed to be taken daily to support a healthy lifestyle, the supplements can also be combined with other longevity ingredients like wheatgerm. Oxford Healthspan’s Primeadine lays claim to being the first spermidine supplement to hit the global market. Other popular options include Hydra Longevity’s Healthy Ageing Essentials and Longevity Labs’ spermidineLIFE.
Read more in our guide to taking longevity supplements.

Safety and side-effects

Considering that spermidine is a naturally-occurring product in the body, it is deemed perfectly safe for health. Additionally, clinical trials suggest that the supplement has no known side effects.

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.

Benefits to health and longevity

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, 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 stabilise 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.

Antiaging effects of spermidine

Spermidine may also be effective in reducing the more physical aspects of aging. One of the earliest signs of aging can be traced in our faces; fine lines, deep wrinkles and sagging skin are seemingly inevitable parts of the aging process, and the common fear of looking older has fuelled the skincare and antiaging industries. Supplements like Oxford Healthspan’s Primeadine promise to solve these skin issues. Based on ancient antiaging wisdom from Japanese medical scrolls, the supplement combines the active ingredients of spermidine and wheatgerm to reduce deep wrinkles and promote hair growth, longer lashes and stronger nails through keratin production, all contributing to a more youthful appearance. Indeed, one study proved the antiaging benefits of spermidine on the skin. It found that spermidine secretions from the Streptococcus bacteria that lives in the skin biome promote production of collagen, elastin and lipids in older skin cells. This improves skin structure and barrier function [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 oestrogen 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-19

The mainstay in medical news over the past few years has been the ongoing COVID-19 pandemic, which has had major implications for longevity, health and wellbeing globally. 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 effected 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 level, 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.