Spermidine is the most abundant polyamine in the body ^[1], and is essential for tissue regeneration, cell growth and cell proliferation. Spermidine is also critical to the processes involved in controlling apoptosis, learning and memory, and binds to and stabilizes RNA and DNA, modulates enzyme functions, preserves and enhances mitochondrial metabolic function and respiration, and has anti-inflammatory properties and antioxidant functions^[2,3,4,5,10].

Spermidine is also a natural inducer of autophagy ^[6], a cytoprotective self-digestive process that assists in removing and recycling damaged and potentially harmful cytoplasmic material that otherwise would accumulate during aging^[7,10].

Spermidine is naturally found in foods such as green peas, chickpeas, cauliflower, broccoli, mushroom and mango in amounts ranging from 25 to 90 mg/kg. Amounts in cheddar cheese, soybean and wheat germ range from 200 to 250 mg/kg ^[8,9]. The majority of spermidine in standard diets comes from whole grains, apples, pears, salad, vegetable sprouts and potatoes^[10].
PlantPills Whole-Food Spermidine has by far the highest spermidine content of any whole food, independently verified to contain over 900 mg/kg (over 0.9mg per gram).
The average person is estimated to consume approximately 10 mg per day ^[10], though this varies from around 7mg to 25mg or more, with the highest amounts present in the Mediterranean diet^[19,20,21].

Tissue spermidine concentrations decline with age ^{[14,15,16,17]}, which may in part be due to a decline in the biosynthetic activities of polyamine-producing enzymes as they become less efficient^[18]. Interestingly, the age-related decline in spermidine levels doesn’t occur in naked mole-rats, that live 10 times longer than other rodent species of the same size^[43].

It has been theorised that because the body produces sufficient spermidine during youth, but not in old age, that spermidine evolves to the status of a vitamin and should be supplemented for health maintenance ^[44].

Spermidine’s ability to induce autophagy ^[6] accounts for many of the effects, due to the key role that autophagy plays in the cellular and molecular mechanisms involved in immune modulation, cardio-protection, neuro-protection, stem cell function and ageing^[22,31]. Alternative mechanisms of action that may be autophagy-independent are direct antioxidant and metabolic effects on increased arginine bioavailability and nitric oxide production^[22], and the MAPK pathway^[45].

Spermidine is classified as a caloric restriction mimetic (CRM) ^[22]. Calorie restriction (CR) is the chronic reduction of calorie intake without malnutrition^[23,24], due in part to the activation of autophagy to maintain proper cell function and promote cell survival under the stress condition of nutrition deficiency^[25].
CRMs potentially mimic the benefits associated with caloric or dietary restriction, in part by inducing autophagy ^[26].

Another CRM, resveratrol, induces autophagy by indirectly activating the “anti-aging” sirtuin enzyme SIRT1 ^[27], whereas spermidine primarily induces autophagy through inhibition of the acetyl transferase EP300. EP300 promotes the activity of mTORC1 (autophagy-inhibitory mechanistic target of rapamycin complex 1). Inhibition of EP300 primarily results in autophagy-relevant cytosolic protein deacetylation. Sustained autophagic control by spermidine is mediated through induction of autophagy relevant gene transcription. This involves the regulation of FOXO transcription factor as well as inhibition of histone acetyl transferases, resulting in epigenetic transcriptional reprogramming^[22].
Spermidine causes mTORC1 inhibition, but also activates phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK), which may further facilitate autophagic response by antagonizing mTORC1 at the functional level ^[41].
The combination of spermidine and resveratrol has shown synergistic effects on autophagy induction ^[28], likely due in part to them initially activating autophagy via different mechanisms.

Pure spermidine is classified as a research chemical, and cannot be used for human consumption, so spermidine can only be supplemented via whole food or extract sources.
PlantPills Whole-Food Spermidine has by far the highest spermidine content of any whole food, independently verified to contain over 900 mg/kg (over 0.9mg per gram). The spermidine content test certificate from the third-party laboratory for the current batch can be seen below.

PlantPills Whole-Food Spermidine is a specific strain of chlorella, a tiny single-celled green alga that lives in fresh water. It's a plant that is about the same size as a human red blood cell, and has existed on earth for over 3 billion years.
Chlorella is very well studied in humans and animals, and is a dietary staple in some parts of the world, with over 7 million people in Japan consuming chlorella on a daily basis.
Our significant experience and expertise with alga has enabled us to cultivate specific strains, that when grown in the correct conditions ^[46], result in the highest whole-food source of spermidine in the world.

Every batch of PlantPills Whole-Food Spermidine is independently verified to have a spermidine content of at least 900mg per kg, with no dangerous levels of heavy metals or micro-organisms. Every single batch is thoroughly tested in-house to confirm the absence of BMAA/microcystin. The certifications for the current batch are viewable below. The current batch of our Whole-Food Spermidine has a spermidine content of 970 mg per kg.

PlantPills Whole-Food Spermidine comes in powder or 250mg tablets. Pack sizes are 250 grams, 500 grams, 1 kilogram, 2 kilograms and 10 kilograms (selectable in the basket).

Independent third party Analysis Certificates

PlantPills Whole-Food Spermidine is a specific strain of chlorella, and it is imperative that chlorella is transported and stored in an oxygen-free environment, even after opening. If chlorella is exposed to oxygen, the nutritional value quickly starts to diminish, because vitamins, enzymes and antioxidants are particularly sensitive to oxygen.

PlantPills Whole-Food Spermidine is supplied in our unique PillFresh™ packaging, which keeps the contents sealed in an environment with an oxygen content of less than 0.1%. After you open your PlantPills Whole-Food Spermidine, just seal it back up, and incredibly, our unique PillFresh™ packaging will again reduce the oxygen content to less than 0.1%, continuing to keep the contents fresh.

This packaging will continue to do this time and time again, for 40 openings.

Other vendors package these types of materials in plastic tubs, or "vacuum sealed" aluminium pouches. Plastic tubs are permeable to oxygen, so are no use for keeping the contents fresh. Tablets in aluminium pouches are difficult to vacuum seal, and this type of vacuum sealing typically contains at least 2% oxygen. This is enough oxygen to start diminishing the nutritional value, and considering mould can grow in air with a 0.3% oxygen content, this really isn't acceptable.

It is therefore pretty certain that a significant amount of nutrition is lost before a typical package of chlorella is even opened by the consumer. Then, after opening, the exposure to oxygen quickly starts to diminish the nutritional value further. While our PillFresh packaging maintains 100% (or very close to 100%) of the nutrients, typical packaging will result in a 37% loss in beta carotene content after four weeks, and an 85% loss in chlorophyll content after 8 weeks.

PillFresh™ packaging is truly innovative, and exclusive to PlantPills.

As pure spermidine cannot be used for human consumption, supplementing with spermidine has to be done via whole foods or extracts naturally containing spermidine. However, very few whole foods or extracts contain spermidine in supplemental amounts.

Until we launched PlantPills Whole-Food Spermidine in 2020, there were only two main spermidine supplements on the market, both of which used wheat germ extract. One from Europe, with one pack containing 60 capsules with an apparent 0.5mg of spermidine per capsule, totalling 30mg per pack, costing around £2 per mg of spermidine. The other from USA, with a pack containing 40 capsules each said to contain 1mg of spermidine, totalling 40mg per pack, costing around £0.85 per mg of spermidine.

Neither of these products has any published third-party laboratory testing for spermidine content, heavy metal content or microbial content.

PlantPills Whole-Food Spermidine is a whole-food, not an extract, and is supplied in packs of 250g powder or tablets (100% product, never any excipients, binders or fillers), containing at least 225mg of spermidine. Depending on the amount purchased, this works out at between £0.06 and £0.08 per mg of spermidine, between 10 and 25 times cheaper than other spermidine supplements.

We also publish third-party laboratory certifications, with spermidine content, heavy metal content and a full microbiological certificate of analysis completed for each batch.

This clearly distinguishes PlantPills Whole-Food Spermidine as the market-leading cost-effective gluten-free spermidine supplement.