Only 5 Best Spermidine Supplements [2023 Review]: Read BEFORE Buying

Is immortality around the corner?

Each new wonder molecule brings us closer.

One hot ingredient in the longevity sector is called spermidine, and it improves six of the nine known tenants of aging. Helping us slow down or even reverse biological aging.

It has quickly become among the hottest anti-aging & longevity supplements. Research suggests spermidine may benefit:

• Youthful look
• Skin, wrinkles, hair, and nails
• Reproductive fertility
• Cardiovascular function
• Immunity
• Inflammation
• Mental health
• Lifespan and healthspan

Right now, spermidine supplements are new. Few companies manufacture it. But before long, cheap knockoffs will flood the market with fake and adulterated products.

Today’s post is a roundup of the latest spermidine research, and how to choose the best spermidine supplement for your lifestyle.

What is Spermidine

Spermidine is an important polyamine (triamine) involved in cellular metabolism. Derived from the amino acid ornithine, and originally discovered in semen, spermidine occurs naturally in the body. Before humans became reliant on chemical agriculture, our produce contained ample spermidine. Levels decline with age, and as it falls, we age faster.

In a nutshell, spermidine is a fasting mimetic with longevity-enhancing benefits (discussed below) similar to caloric restriction, the gold standard of increasing lifespan. It works by activating AMPK and increasing the vital process of cellular repair (called autophagy). It also protects DNA and mitochondria, acts as a signaling molecule, and has countless other benefits (discussed below).

We can help mitigate spermidine deficiency by consuming foods rich in spermidine. But unless you like foods best described as “acquired tastes”, you’ll want the ease of spermidine supplements.

Studies on this supplement show great bioavailability and an outstanding safety profile. Participants in clinical trials have not reported side effects, which makes sense since it’s naturally found in the body. Some researchers believe that…

Spermidine will eventually receive classification as an essential nutrient Click To Tweet

Although there’s little research on the optimal time to take spermidine, it likely works best when taken with food. This is because, prior to supplementation, spermidine traditionally came packaged within whole foods.

After discussing the top spermidine products next, we’ll cover the health benefits and mechanisms. Or you can click here to skip to them now.

The Best Spermidine Supplements of 2023

I’m a proponent of maximizing nutrition from diet.

That said, Western food notoriously lacks spermidine and other polyamines. Many of the foods naturally high in it (discussed later) are “acquired” tastes. Textures and tastes that I’d rather not experience.

For me at least, that leaves supplementation.

But few companies manufacture spermidine, so supplements are expensive. Soon enough, more facilities will process spermidine, and the current premium will disappear. Remember, just a few years ago it was only available through research chemical vendors.

Companies selling spermidine will surely sprout up everywhere. Here’s what you should look for when purchasing high-quality spermidine:

• Dose — most trials so far have used ~1mg, but up to 8mg per day appears safe
• Organic — it gets extracted from various foods, and GMO products concentrate toxins
• Scientific Advisory Board — product formulations and dosing should reflect the latest research
• Junk — companies cut corners and use harmful excipients, flow agents, binders, and fillers, which you can avoid by checking the label
• Facility — products should be produced to GMP and ISO9001 standards
• Form — it comes in powder, topical, tablet, and capsule form, each with pros and cons

Let’s get started.

Benefits of Spermidine

Now, we’ll discuss what spermidine does.

Though researchers have investigated spermidine since 2002, interest accelerated with the discovery of autophagy in 2016.

Today, over 13,447 studies have highlighted the immense potential of spermidine.

I’ve compiled some of the findings here.

Potent autophagy booster

Spermidine profoundly increases the cellular maintenance process called autophagy. As well as the same process occurring in the mitochondria (mitophagy).

Many of the most notable benefits likely stem from recycling misfolded proteins and faulty structures.

Early 2010 spermidine research hypothesized that “increased autophagic turnover of cytoplasmic organelles or long-lived proteins is involved in most if not all life span-prolonging therapies”.

Increasing autophagy slows damage accumulation and extends healthspan.

Anti-inflammatory

Inflammation plays a role in virtually every degenerative condition.

Spermidine is well known to both block inflammation, and exhibit anti-inflammatory mechanisms (increases cytokine IL-10).

It “reduces inflammaging-associated cytokines IFN-γ, IL-1β, IL-6, and TNF-α” and IL-12, in mice at least.

Spermidine also inhibits inflammation stimulated by the toxin LPS. It does so by “blocking the NF-κB, PI3K/Akt and MAPKs signaling pathways in microglia”.

This supplement can quell cytokine storms and stop the inflammatory cascade that leads to many conditions.

Spermidine’s anti-inflammatory mechanisms result in greater resilience to age-associated diseases.

Circadian reset

Surprisingly, spermidine is a potent circadian rhythm regulator.

A newer 2021 study found that just 60 minutes after ingestion, this supplement modulates the expression of “clock genes”. Kicking in even faster than the autophagic benefits.

The authors concluded,

“…spermidine is a potent modulator of the circadian phase, acting through glucocorticoid receptor-independent pathways, and may be useful for treating diseases related to circadian desynchrony.”

Spermidine resets circadian clock phase in NIH3T3 cells

When I can’t entrain my circadian rhythm naturally with early morning light exposure, I’ll take spermidine instead.

Improves cognitive function & slows decline

Dietary spermidine can pass through the blood-brain barrier and exert effects on the brain.

Multiple trials in older adults found nutritional spermidine has a positive impact on memory performance.

Preliminary research in aged mice has found that it helps the brain generate energy more effectively, improves memory, and enhances other facets of cognition:

• Improves behavior
• Better spatial learning
• Improved dementia
• Greater memory and slower deterioration

I find memory preservation especially interesting, as dementia is a chief symptom of aging.

Another late 2020 paper found high spermidine intake in adults to be a promising brain health strategy.

New research around spermidine and mental health is still making headlines.

Prevents neurotoxicity

A few studies have investigated the effect of spermidine on toxicity in the brain.

The most interesting of which, was a study of rats exposed to the toxin sodium laurate. Predictably, the control group developed cerebral small vessel disease (CSVD). Pathological symptoms included:

• Arterial damage
• Mitochondrial impairment
• Autophagic hyperactivity

Feeding spermidine to the other group protected against these effects, with researchers noting, “maintenance of mitochondrial stability and proper autophagy activity.”

Other trials have found similar neuroprotective effects.

Improves TBI recovery

Mouse research in 2020 observed the role of spermidine and brain injury.

Researchers discovered a strong inverse correlation between TBI severity and spermidine level.

The lower your spermidine level, the worse the TBI (and vice-versa).

Spermidine appears to influence the blood-brain barrier and the rate of neuronal cell death. Inhibiting spermidine synthesis negatively impacted neurobehavioral recovery.

They concluded,

“For the first time, we demonstrated that administrating spermidine may provide a new treatment for TBI.”

Spermidine Exhibits Protective Effects Against Traumatic Brain Injury

Those that engage in contact or collision sports should stay abreast of the link between spermidine and concussions.

Caloric restrictions benefits without fasting

Autophagy is one of the primary benefits of fasting.

Researchers have long since considered spermidine a fasting mimetic. It provides many of the same benefits without the torture of restriction.

But that’s not all.

Another spermidine benefit is optimized genetic expression,

“..increased intake of the polyamine spermidine appears to reproduce many of the healthful effects of caloric restriction, and they explain its cellular actions, which include enhancement of autophagy and protein deacetylation.”

Spermidine in health and disease

Protects against degenerative disease

In addition to neuroprotection, spermidine protects against other diseases.

These protective effects include:

• Cancer
• Metabolic disorder
• Heart disease
• Impaired movement
• Osteoarthritis
• Chronic kidney disease
• Liver damage

This is another promising area of research.

Though spermidine may help protect against cancer, several papers show that it can accelerate tumor growth once established.

Protects mitochondria and telomeres

Spermidine has profound effects on the mitochondria.

This 2020 paper found much of the anti-aging benefit comes from improving both autophagy and mitochondrial function.

Another paper showed spermidine helped protect mitochondria against cell aging and destabilization when treated with a toxin.

The mitochondria have their own version of autophagy (called mitophagy), and spermidine improves the process. It also increases the creation of new mitochondria through a process called mitochondrial biogenesis.

Spermidine also shifts the energy balance of the cell by activating AMPK.

Then this 2021 research showed that spermidine slows down telomere shortening.

Healthy mitochondria lead to healthy humans.

Slows biological aging in humans

Original spermidine research showed slowed aging in other organisms.

Yeast, nematodes, flies, and mice all lived longer when fed spermidine-rich diets.

Then, in 2018, research (mostly epidemiological) found similar correlations in humans too.

In fact, levels of the entire polyamine family have strong associations with aging and disease. They also confer increased resiliency against stress.

Autophagy, geroprotection (DNA), AMPK activation, mitochondrial protection, and other mechanisms all combine to exert spermidine’s anti-aging effect.

Beauty (skin, hair, nails)

Not only does it have potent longevity benefits, but spermidine notably improves the skin, nails, and hair.

Emerging data on spermidine makes it a promising beauty-enhancing supplement for:

• Skin elasticity
• Skin hydration
• Skin desquamation
• Hair growth

Researchers postulate that the beauty benefits come from restoring the collagen and lipid synthesis of aged cells. Resulting in improved skin structure and function. Much of this likely occurs through the skin microbiome.

Several studies have also found that spermidine speeds up hair growth, and slows down hair loss.

I haven’t noticed any real beautification changes yet, but I’ve already seen commercial interest in topical creams fortified with spermidine.

Immune health

Spermidine improves immunity through various mechanisms.

Immunity is also linked to inflammation and autophagy.

One mouse study compared spermidine to the immunosuppressive yet popular longevity drug rapamycin. Old mice generally create fewer antibodies as a result of illness or vaccination. Researchers found giving these mice spermidine restored T cell antibody response to healthy levels.

Other research suggests improved T-cell and B-cell function, as well as helping quell immune system overactivation (autoimmunity).

Spermidine appears to restore immune function back to homeostasis.

Promotes heart health

Spermidine plays an integral role in protecting the cardiovascular system.

Research has indicated that spermidine improves:

• Blood pressure
• Cardiovascular disease risk
• Death related to heart disease
• Cardiac hypertrophy
• Heart failure progression
• Cholesterol

One study suggests that the cardioprotective benefits of spermidine come from the following mechanisms (emphasis mine),

“…stimulation of autophagy, mitophagy and mitochondrial respiration and improved the mechano-elastical function of cardiomyocytes”. Beneficial effects of spermidine on cardiovascular health and longevity suggest a cell type-specific import of polyamines by cardiomyocytes

Spermidine also increases levels of a potent cardioprotective molecule called Nitric Oxide (NO).

It may prevent fat gain and reduce cholesterol through changes to VSMCs, again, driven by autophagy.

Spermidine seems like a great preventative strategy to protect your heart and arteries.

Mitigates damage from drinking alcohol & toxin exposure

A 2021 mouse study found that spermidine can reduce toxicity caused by alcohol and other compounds.

Drinking causes systemic toxicity via dehydration and the toxin acetaldehyde.

This paper investigated how spermidine impacts:

• LPS-induced oxidative stress
• Lipid peroxidation
• Ethanol toxicity

One mechanism behind spermidine’s antioxidant role is via suppressing inflammation.

Researchers of that study concluded,

“Together, our results indicate that spermidine is an antioxidant thereby conferring anti-inflammatory and anti-fibrotic effects associated with alcoholic liver injury.”

Spermidine Prevents Ethanol and Lipopolysaccharide-Induced Hepatic Injury in Mice

Anti-obesity effects

Spermidine has anti-obesogenic properties.

It activates autophagy and mitophagy, protects the heart and mitochondria, and even prevents the creation of new fat (lipogenesis).

Obese rats on a high-fat diet that were fed spermidine had some impressive benefits:

• Fat breakdown
• Inflammation
• Gut barrier function
• Conversion of fat into heat energy

Eight weeks of spermidine treatment led to less fat mass, better blood labs, reduced inflammation, more fat-burning brown adipose tissue, and a healthier gut. The team concluded,

“These findings demonstrate that spermidine has potentials in treating obesity.”

Spermidine ameliorates high-fat diet-induced hepatic steatosis and adipose tissue inflammation in preexisting obese mice

Lengthens healthspan

Many of the discussed mechanisms promote a longer lifespan.

One study followed 829 participants for 15 years and divided the groups by dietary spermidine consumption. Their analysis uncovered a 5.7-year lifespan difference between groups consuming the most and least spermidine.

Follow-up research found increased lifespan in cancer patients, cardiovascular disease, and those with other degenerative conditions.

We may have the effect reversed. It seems plausible that spermidine deficiency artificially decreases lifespan.

Either way…

Consuming adequate spermidine seems to increase both lifespan and the quality of those years (called healthspan).

Spermidine vs Other Longevity Supplements

Spermidine isn’t the only anti-aging compound taking the world by storm.

Here’s how spermidine compares and differs from some of the most popular longevity supplements.

Spermidine vs Fisetin

Fisetin is a bioflavinoid plant pigment and antioxidant recognized for its senolytic and DNA-protective properties. It’s naturally found in fruits and vegetables. Like spermidine, fisetin induces autophagy, inhibits inflammation, and may extend healthspan.

Fisetin, however, has considerably less human research, is more expensive, and is harder to find than spermidine. Due to their similar effects, an ideal supplement would contain a synergy of both spermidine and fisetin. Click here to learn more about fisetin.

Spermidine vs Rapamycin

Rapamycin is a potent immunosuppressive pharmaceutical drug that has received attention for its longevity-enhancing effects. It works primarily by inhibiting the mTOR pathway of cellular growth and repair. This activates AMPK and autophagy. Suppressing the immune system comes with a host of side effects.

Unlike spermidine which has zero side effects and many of the same benefits, Mayo Clinic lists over 100 side effects of rapamycin (also called Sirolimus). Rapamycin should only be used under close doctor supervision, and in precise cycles. As a dietary nutrient, spermidine is a safer choice. It also does not come at the cost of increased frailty and the inability to build lean body mass.

Spermidine vs NMN

Spermidine and NMN are the most popular longevity supplements available. Both increase healthspan, activate autophagy, protect cognitive function, boost the immune system, and improve cardiovascular function.

Spermidine improves more aging pathways (six out of all nine) and appears to be better for beauty (skin, hair, nails) than NMN. NMN seems better able to stave off cognitive decline and restore youthful energy levels. A smart supplementation program includes both NMN and spermidine. Click here to learn more about beta-NMN.

Common Spermidine Questions & Answers

Spermidine: Should You Take This Longevity Supplement?

Spermidine is rapidly becoming a household name.

Key to improving your quality of life, staving off age-related decline, and thriving. It combines nicely with other longevity molecules and has virtually zero side effects.

It’s one of few compounds that improve SIX of all nine aging pathways. Thousands of studies have led many researchers to believe that…

Spermidine will soon become a required dietary nutrient.

One virtually absent from our modern diet. Unless you eat piles of natto.

But you must know that not all spermidine supplements are equal. Many contain more fillers and contaminants than active ingredients.

Imagine the tragedy of a fake spermidine product actually shortening your healthspan.

That’s why I’ve researched and reviewed the best spermidine supplements on the internet:

• Best overall spermidine: Primeadine
• Best researched spermidine: spermidineLIFE
• Best value spermidine: DoNotAge

Do you take spermidine? Let me know your experience in the comments below and let’s make this a conversation!