What Causes Low Spermidine Levels?

Spermidine is a powerful polyamine that promotes autophagy, the body’s cellular “clean-up” process, and inhibits 9 of the 12 scientifically identified root causes of aging, known as the “Hallmarks of Aging.” While two-thirds of the body’s spermidine is produced by the gut and body tissues, the remaining third comes from food. As we age, natural spermidine production declines, so maintaining youthful levels requires external sources, either from spermidine-rich foods or supplements like Primeadine.

Studies link higher levels of spermidine with longevity. Human trials show that food-derived spermidine supports cognition, heart health, hormonal balance, hair growth, collagen production, and nail strength, with potential benefits for fertility and circadian rhythm. These effects stem from spermidine's ability to trigger autophagy—the body's cell renewal process—and inhibit nine of the twelve "Hallmarks of Aging," including inflammation, stem cell and mitochondrial dysfunction, and gut imbalance. Clients also report deeper sleep, increased energy, gray hair reversal, improved skin, and better gut health. Read this blog post to learn more.

The key differences between food-derived and synthetic spermidine lie in their absorption, bioavailability, and overall effectiveness:

Bioavailability & Absorption

• Food-derived spermidine comes with beneficial, naturally co-occurring polyamines, called spermine and putrescine, that are involved in the Polyamine Salvage Pathway - a virtuous recycling loop that helps your body make more spermidine. These additional polyamines also have unique benefits their own and play a role in many of the proven benefits of spermidine. 
• Synthetic spermidine is isolated and lacks these natural co-factors, reducing bioavailability.

Handedness

• Humans have co-evolved with plants, and our bodies recognize the natural, 3-dimensional molecules from plants.
• Synthetic spermidine is a flat, 2-dimensional chemical mimic, but molecules are 3-dimensional.  While our bodies can identify some parts of synthetic versions, they aren't the same—like trying to fit a right hand into a left-handed glove.

Food Matrix Effect

• In whole foods, spermidine interacts with other nutrients in a way that enhances its stability and uptake.
• Synthetic versions do not have this advantage. 

Gut Microbiome Interaction

• Certain gut bacteria help metabolize spermidine from food sources, improving its utilization.
• Synthetic spermidine does not engage gut bacteria in the same way, leading to less efficient absorption.

Purity & Safety

• Food-derived spermidine is naturally sourced, making it a cleaner and safer option. It is the only kind to be tested for safety and efficacy in humans.
• Synthetic spermidine has not been tested for safety and efficacy in humans, so we don’t know if it’s safe to take long-term. It is used by companies that don’t value quality and safety, so it typically comes with additional fillers, additives and other unhealthy ingredients.

Efficacy & Longevity Benefits

Because of its natural composition and bioavailability, food-derived spermidine is  considered more effective in promoting autophagy and supporting longevity.

If a spermidine supplement claims to be food-derived but is cheap and offers a high dose, don't be fooled!

We've tested other spermidine products labeled as 'wheat germ with spermidine' and found that they often mix a small amount of wheat germ with large quantities of synthetic spermidine. These low-cost, high-dose options offer no guarantee of safety or effectiveness.

While we can’t speak directly about the formulation of other spermidine products, here are some of the main differentiators of Primeadine®/Oxford Healthspan.

• We source our raw materials from Japan, which is known for its Nobel Prize-winning scientific leadership on autophagy, or cell renewal. Japan has the most rigorous quality control and testing policies in the world, meaning our ingredients have the most advanced extraction process and meet the incredibly high standards of the Japan Health Food and Nutrition Food Association. They are tested for heavy metals, mold, fungi, and bacteria at the Japan Food Research Lab (JFRL), a third party independent testing lab.
• Every single batch is tested for its amount of food-derived spermidine so we ensure it contains the minimum effective dose of 1mg stated on our labels.
• Primeadine® is manufactured in Japan in an FDA-registered and -inspected facility with ISO22000 standards, the highest in food quality control. It is then encapsulated in an FDA cGMP facility in the USA and undergoes purity testing there as well at Eurofins or Delta.
• Our capsules and tablets do not contain any synthetic ingredients, whereas other supplements typically contain magnesium stearate (of which circa 80% has hydrogenated fats in it; the supplement industry is not legally required to get rid of hydrogenated oils the way the processed food industry has been mandated by law to), shellac, talc and glycerin. Our products are all suitable for vegans. Learn more about our sourcing, quality, and testing standards.
• The Primeadine® Original formulation includes a special type of prebiotic fiber, called FOS (fructooligosaccharide), that selectively feeds the friendly, spermidine-producing bacteria in the gut microbiome. The idea is to increase both supplemental, or 'exogenous' spermidine, as well as encourage your own body's natural ability to produce spermidine in your gut microbiome.
• Primeadine® GF comes from a sub-strain of chlorella singled out from over 100 others because it alone contains a high level of spermidine and also contains putrescine, the precursor polyamine to both spermine and spermidine. Our chlorella is grown in the nutrient-abundant longevity islands of Okinawa, Japan, and exposed to sunlight to increase the chlorophyll and other nutrient content, such as vitamins D and K, which together help drive calcium to the bones. We combine the chlorella with two other anti-inflammatories and autophagy inducers, Okinawan turmeric and nobiletin (from Okinawan "Shikuwasa" citrus lime peel).
• We do not use liposomes in Primeadine® because this is unnecessary for absorption and would prevent the benefits that happen when spermidine is exposed directly to the gut lining. There is no evidence that spermidine cannot be taken up by the cells on its own. Similar to amino acids, polyamines do not need a liposome to cross into the cell or to be taken up with epithelial cells. The process of creating a liposomal version also creates unnecessary expense.
• We do not synthetically enrich our product with synthetic spermidine. Be wary of labels that say "wheat germ with spermidine" as this indicates that the wheat germ has been soaked in synthetic spermidine, thereby increasing the overall amount of spermidine but meaning it is no longer a natural source.
• We do not use doses beyond what the European Food Safety Authority (EFSA) has mandated as safe for human consumption, which is 6mg daily. Please note that this is related to food-derived spermidine. Synthetic spermidine and synthetically enriched spermidine have never been tested in humans for safety or efficacy and are being sold without regulatory oversight. 
• We work closely with our scientific and clinical advisers at the University of Oxford and abroad, all of whom take our product and share it with their loved ones. Learn more about our scientific advisory board here.
• We are also the only non-Japanese member of the Japan Autophagy Consortium, whose Senior Adviser is the 2016 Nobel Prize Winner in Medicine or Physiology, Prof Yoshimori Ohsumi, and whose Director is Prof Tamotsu Yoshimori, Osaka University. Prof Yoshimori conducted all of the mammalian research in autophagy that helped underpin Prof Ohsumi's work in yeast cells. Find out more about our story here.

The US FDA has not set a safe upper limit for food-derived spermidine, but the European Food Safety Authority considers up to 6 mg safe. Most studies use a daily dose of 1 mg of natural spermidine, along with spermine and putrescine, which are absent in synthetic versions. Synthetic spermidine has not been tested for human safety or efficacy.

We prioritize the highest quality, avoiding common additives like industrial seed oils, magnesium stearate, and talc often used in supplements. Unlike cheap synthetic spermidine often "cut" into products, we use food-derived spermidine sourced and manufactured in Japan under strict regulatory standards. Our products undergo rigorous third-party testing to ensure purity and effectiveness. This commitment to quality, like choosing the best ingredients for a child’s birthday cake, is our guiding philosophy.