Is immortality around the corner?
Each wonder molecule discovered brings us closer.
One of which is an ingredient 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
- Mental health
- Lifespand 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 2022
I’m a proponent of maximizing nutrition from our 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 — spermidine 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 — spermidine comes in powder, topical, tablet, and capsule form, each with pros and cons
Let’s get started.
Dose: 1mg spermidine
Spermidine Source: 910mg wheat-germ extract
Other Ingredients: FOS prebiotic fiber
Inactive Ingredients: Plant cellulose capsule
Manufactured In: USA
Servings: 30 (90 capsules total)
Ships To: Global
Price: $90 (save 10% with code URBAN10)
Best For: Stimulating the body's natural production
After working with elite Oxford scientists, Leslie Kenny founded Oxford Healthspan which was one of the first spermidine supplements commercially available. Their spermidine comes from highly concentrated Japanese wheat germ.
Oxford Healthspan's raw materials pass the rigorous standards of the Japan Health Food and Nutrition Food Association. Japan’s known for its Nobel prize-winning autophagy research.
Their formula sets Primeadine apart from the rest. First, they avoid all synthetic ingredients and unnecessary fillers. Many of which are not vegan-friendly. While Oxford Healthspan sources raw ingredients from Japan, the final product is made in an FDA cGMP-Certified facility before it undergoes additional purity testing.
Next, they’ve included a unique prebiotic fiber that feeds the gut’s spermidine-producing bacteria (Fuso- and Bacteroides). Increasing your spermidine levels through supplementation and also teaching your body to produce more naturally.
Primeadine’s marketing has focused on the supplement’s aesthetic-enhancing properties like fuller hair, faster nail growth, glowing skin, reduced wrinkles, and better eyelashes. Indeed, research has substantiated their claims. If you browse the internet or talk to enough biohackers, you’ll surely come across real-world reports of Primeadine upgrading beauty routines.
This was the first spermidine supplement I tried, and I still have several bottles on my shelves. Primeadine is the only product that also increases your body's natural spermidine-producing healthy bacteria.
Use the exclusive Primeadine code URBAN10 for 10% off
Dose: 1.5mg spermidine
Spermidine Source: 800mg wheat-germ extract
Other Ingredients: 1.5mg zinc, 0.2mg thiamine
Inactive Ingredients: Plant cellulose capsule, acetylated starch, calcium carbonate, magnesium stearate, glycerol
Manufactured In: Austria
Servings: 30 (60 capsules total)
Ships To: Global
Price: $99 (save 15% with code URBAN15)
Best For: Used in real clinical research
Based out of Austria, Longevity Labs’s spermidineLIFE is the other major spermidine brand, backed by some of the most famous longevity researchers. Their Scientific Advisory Board includes the prestigious Dr. David Sinclair (who popularized NMN and NR supplements), Guido Kroemer — the most cited autophagy researcher, and many others.
LIFE is the first and only award-winning spermidine supplement that’s currently in use by 80+ international research teams. Since their 2019 founding, most clinical research has used and relied on these products.
spermidineLIFE sells three products:
- spermidineLIFE Original
- spermidineLIFE Memory +
- spermidineLIFE Immunity +
As you’d expect, spermidineLIFE is a vegan-friendly, non-GMO wheat germ extract free of contaminants.
All feature the same 800mg of wheat germ extract containing 1mg of spermidine.
- Memory Plus also has cognitive-enhancing micronutrients, the Ayurvedic herb Brahmi, and mood-boosting Saffron extract
- Immunity Plus contains immunomodulatory vitamins and minerals, and adaptogenic shiitake mushroom
I have two bottles of spermidineLIFE sitting next to me which I will test after I finish Primeadine. This product is for those that want the same spermidine used in academic research and don’t mind paying a slight premium.
Use the exclusive spermidineLIFE code URBAN15 for 10% off
Do Not Age Spermidine
Do Not Age Spermidine Overview
Dose: 4mg spermidine
Spermidine Source: 400mg wheat-germ extract
Other Ingredients: 1mg zinc
Inactive Ingredients: Cellulose
Manufactured In: UK
Servings: 60 (60 capsules total)
Ships To: Global
Price: $69 (save 10% with code URBAN)
Best For: Guaranteed potency
UK-based Do Not Age (DNA) is another popular vendor of longevity supplements. They’re best known for their sirtuin-activating supplements (SIRT6 activator in particular). I’ve talked to their Founder, Alan Graves, and the company prioritizes producing high-quality yet affordable supplements. To decide which products to offer, Do Not Age reviews the literature and surveys their customers. That's exactly what led them to produce the best value spermidine.
What makes this one stand out is that just 400mg of wheat germ extract provides a huge 4mg of spermidine. And you also get 1mg of Zinc Picolinate. That’s 4X more potency in one capsule than many of the others. All without crossing into the safety gray area.
Do Not Age sells their vegan-friendly spermidine in two quantities:
- 60 capsules for $69
- 366 capsules for $375
They produce their spermidine to GMP and ISO9001 standards and then store them in optimal environments.
Most companies lab test their products and then store them in hot, light, humid warehouses which oxidizes and degrades the supplement. By the time you receive your average spermidine product, it may have little potency remaining. As with all their products, DNA guarantees that you’ll actually receive maximum quality and purity on your doorstep. And they ship worldwide.
Do Not Age spermidine is the best overall value in terms of quality and potency.
Use the exclusive DoNotAge code URBAN for 10% off
Double Wood Spermidine
Double Wood Spermidine Overview
Dose: 10mg spermidine
Spermidine Source: Putrescine
Other Ingredients: None
Inactive Ingredients: Plant cellulose capsule, rice flour
Manufactured In: Unknown
Servings: 60 (120 capsules total)
Ships To: Global
Best For: Tight budgets
If you take longevity supplements, you’ve probably heard of Double Wood. They were the company to make the wildly-popular NMN more affordable to consumers. Companies like Double Wood do not disclose nearly as much information around their processes, purity, or safety testing.
They claim that their capsules are manufactured and lab-tested in the USA. The lab testing is for the weight and heavy metal content. We don’t know about purity. The label also states that they’re non-GMO and gluten-free.
Most brands use wheat germ for their spermidine. Double Wood synthesizes spermidine from Putrescine. Very little research has investigated Putrescine-derived spermidine, so do not know the bioavailability of this method nor how the benefits compare.
Containing 10mg in one serving, this is the strongest spermidine supplement I could find. At first glance, that may seem appealing. Note that we don't have data for humans consuming 10mg+ of spermidine daily. It may be safe.
Each bottle contains 120 capsules. Since a serving is two capsules, each contains 5mg of spermidine. Double Wood does use rice flour as a filler.
If you’re willing to take a risk and want the cheapest spermidine, look into Double Wood.
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 autophaghy 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.
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.
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:
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.
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.
“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:
- Metabolic disorder
- Heart disease
- Impaired movement
- Chronic kidney disease
- Liver damage
This is another promising area of research.
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.
Delays 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.
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
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 roles is by 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
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
- 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
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.
We may have the effect reversed. It seems plausible that spermidine deficiency artificially decreases lifespan.
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.
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.
Common Spermidine Questions & Answers
What are natural sources of spermidine?
The foods naturally highest in spermidine include wheat germ, natto, mushrooms, cauliflower, soybeans, broccoli sprouts, and other plants. While not a food, sperm also contains high levels of spermidine, spermine, and other polyamines.
What is the best spermidine dose?
Research suggests that consuming 1-7mg of spermidine daily is safe in humans and other animals. Most research recommends 1-2mg, and few suggest doses of 7mg+.
Is spermidine safe or risky?
Studies suggest that in normal doses, spermidine is safe both in humans and other animals. So far clinical trials have not found any adverse side effects. Some researchers believe spermidine will soon get reclassified as an essential nutrient.
How long do the benefits of spermidine take to work?
The benefits of spermidine take about 2 months to start showing and continue to accumulate with regular use.
Spermidine: Should You Take This Lonegvity 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 ingredient.
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!