Ingredient Reference
Spermidine: Chemistry, Food Sources, Studied Amounts and Safety
A reference page on what spermidine is, how the body makes it, where supplement spermidine comes from, how to read a label, what amounts human studies used, and who should check with a clinician first.
See Urolithin A + SpermidineSpermidine on the Label
The planned amounts in our capsules, per serving of 2 capsules.
Status: Planned formula. Join the waitlist and we will email you when it launches. No payment is taken. How to use it: the serving is 2 capsules; follow the label directions once it launches. Why the source matters: many spermidine supplements are made from wheat germ, while this formula's spermidine is planned to come from a gluten-free source. How this compares with research amounts: the 3 and 12 month trials used 0.9 to 1.2 mg a day from wheat germ extract, and two short absorption studies used 15 and 40 mg a day.
Spermidine at a Glance
| Item | Details |
|---|---|
| Chemical name | N1-(3-aminopropyl)butane-1,4-diamine; formula C7H19N3. |
| Family | Polyamines, with putrescine and spermine. |
| Richest foods measured | Wheat germ (2,437 nmol/g) and soybeans (1,425 nmol/g). |
| Diet supplies | About 87 micromoles a day in EU adults, roughly 12.6 mg. |
| Supplement studies | 0.9 to 1.2 mg a day for 3 to 12 months; 15 and 40 mg a day for up to 28 days. |
| Main cautions | Wheat sources and gluten, pregnancy and breastfeeding, cancer care, prescription medicines. |
| US status | Sold as a dietary supplement. FDA does not approve supplements before sale. |
Here for the benefits? Autophagy, the long-term diet research and the memory trials in plain terms are covered in Spermidine: Benefits, Foods, Side Effects and Dose. This page sticks to reference facts.
What Spermidine Is: Polyamine Chemistry
Polyamines are small molecules with two or more amino groups. At the body's pH they are fully protonated, so they carry positive charges and bind tightly to negatively charged DNA and RNA. They play an essential role in cell growth and proliferation.
| Polyamine | Amino groups | How cells make it | In food |
|---|---|---|---|
| Putrescine | 2 | From the amino acid ornithine, by ornithine decarboxylase (ODC) | Varies widely; green pepper measured 794 nmol/g |
| Spermidine | 3 | Spermidine synthase adds an aminopropyl group, taken from decarboxylated S-adenosylmethionine, to putrescine | The main polyamine in plant foods |
| Spermine | 4 | Spermine synthase adds a second aminopropyl group | Generally higher in animal foods, though wheat germ has 722 nmol/g |
Recycling between the three
Cells can run the pathway backward. An N-acetyltransferase first tags spermine or spermidine with an acetyl group, then polyamine oxidase removes a propylamine group, giving back spermidine or putrescine. Diamine oxidase and polyamine oxidase handle final breakdown. This interconversion helps explain why a spermidine supplement can show up in blood as spermine.
Three sources for the body
The body gets polyamines from its own synthesis, from food (and breast milk in infancy), and from gut bacteria, mainly in the large intestine. Synthesis tends to decrease with age, and cellular spermidine and spermine levels and ODC activity tend to fall during aging.
Wheat Germ Extract, Other Sources and Labels
| Source or form | What it is | What to know |
|---|---|---|
| Spermidine-rich wheat germ extract | An extract of non-fermented, non-sprouted wheat germ (Triticum aestivum) | The form in the 3 and 12 month trials. It is a wheat ingredient and carries other polyamines too. |
| Blends from other plants | For example, the product in the 15 mg study was based on Chlorella algae powder and soybean extract | One route to a wheat-free source; the label should name it. |
| High-purity spermidine trihydrochloride | A purified salt of spermidine | Used at 40 mg a day for 28 days. Salt weight is higher than spermidine weight. |
| Food | Wheat germ, soybeans, mushrooms and some aged cheeses | Amounts vary by food, origin and ripening. |
Extract weight is not spermidine weight
In the 3 month safety trial, 750 mg a day of wheat germ extract supplied 1.2 mg of spermidine, along with 0.6 mg of spermine and 0.2 mg of putrescine. A label that gives only the extract amount does not tell you the spermidine dose. Details worth finding:
- Spermidine in mg per serving, stated separately from the extract weight.
- The source: wheat germ, soy, algae or another plant, or a purified salt.
- Salt form: whether the figure refers to spermidine or to spermidine trihydrochloride.
- Allergen and gluten-free statements if you avoid wheat or gluten.
- Other polyamines such as spermine and putrescine, if listed.
Measured amounts in foods
A 2019 review of polyamines in food put wheat germ at 2,437 nmol/g and soybeans at 1,425 nmol/g of spermidine. Vegetables ranged from 6.9 to 398 nmol/g. Most cheeses were under 69 nmol/g, with one blue cheese at 262 nmol/g. A 2023 study gave cheddar at about 200 mg/kg and mushrooms at about 90 mg/kg.
Spermidine in Human Studies
Randomized, placebo-controlled studies of spermidine supplements, all in adults.
| Study | Who | Amount a day | Length | Measured | Result |
|---|---|---|---|---|---|
| Schwarz 2018, Aging | 30 adults aged 60 to 80 with subjective cognitive decline | 1.2 mg, from 750 mg wheat germ extract | 3 months | Vital signs, weight, blood chemistry, blood counts, self-rated health, compliance | No group differences in safety measures; compliance about 98% |
| Wirth 2018, Cortex | The same 30-person trial | 1.2 mg | 3 months | Mnemonic similarity task (memory) | Scores improved from baseline in the spermidine group, a medium effect; authors called for a larger trial |
| Schwarz 2022, JAMA Netw Open | 100 adults aged 60 to 90 with subjective cognitive decline | 0.9 mg, from wheat germ extract | 12 months | Memory change (primary), other cognitive and biomarker outcomes | Primary and secondary scores similar between groups; exploratory analyses pointed to verbal memory and inflammation markers; adverse events similar |
| Senekowitsch 2023, Nutrients | 12 healthy adults aged 21 to 45 | 15 mg, from an algae and soybean based product | 5 days per phase, crossover | Plasma and saliva polyamines, blood metabolites | Plasma spermine exposure rose versus placebo; plasma spermidine and saliva levels unchanged |
| Keohane 2024, Nutr Res | 37 healthy men aged 50 to 70 | 40 mg spermidine trihydrochloride | 7 and 28 days | Serum and urine polyamines, clinical and blood tests | No substantial change in serum or urine polyamines; no product-related adverse events |
Studied Amounts and Dietary Intake
Amounts from research and regulators, not directions. Follow your product's label.
| Setting | Amount of spermidine |
|---|---|
| Long trials, wheat germ extract | 0.9 to 1.2 mg a day for 3 to 12 months |
| Short absorption studies | 15 mg a day for 5 days; 40 mg a day for up to 28 days |
| Diet, EU adults (Spain highest) | 87 micromoles a day, about 12.6 mg (Spain 103 micromoles, about 15 mg) |
| Diet, US adults aged 40 to 80 | 54.7 micromoles a day, about 7.9 mg |
| Diet, Japan | 74 micromoles a day, about 10.7 mg |
| EU and UK limit, wheat germ extract in supplements | Up to 6 mg a day for adults |
| Official recommended intake | None set |
A 2023 study put average European intake at about 10 to 15 mg a day. Milligram figures for diets here are converted from the micromole values in the 2019 review.
Safety, Side Effects and Who Should Ask First
At 1.2 mg a day for 3 months, vital signs, weight, blood chemistry and blood counts did not differ from placebo. Over 12 months at 0.9 mg, adverse events were similar in both groups. At 40 mg a day for 28 days, clinical, lipid, chemistry and blood count results did not change versus placebo, and no product-related adverse events were reported.
- Wheat and gluten: wheat germ extract is a wheat ingredient. Check the source and allergen statement.
- Cell growth: elevated polyamine levels in people with cancer are associated with tumor growth, so anyone in cancer care should ask their oncologist first.
- Pregnancy and breastfeeding: the EU and UK authorization for wheat germ extract excludes pregnant and lactating women. Ask your clinician.
- Under 18: the studies above enrolled adults only.
- Medicines: these trials did not test drug interactions, so ask a clinician before use if you take any prescription drug.
Stop taking it and contact a clinician if you notice signs of an allergic reaction, such as hives, swelling or trouble breathing.
Regulatory Status in the US
In the US, spermidine is sold in dietary supplements under the Dietary Supplement Health and Education Act of 1994 (DSHEA). FDA does not approve supplements before they are marketed; the maker or seller is responsible for safety and labeling.
For conventional foods, a GRAS notice (GRN 889) proposed spermidine-rich wheat germ extract for food bars and yogurt drinks at up to 2.7 g per serving. FDA closed it on March 20, 2020, after ceasing its evaluation at the notifier's request, so no "no questions" letter was issued.
For comparison, the EU and UK authorize spermidine-rich wheat germ extract as a novel food for food supplements, at up to 6 mg of spermidine a day, for adults excluding pregnant and lactating women, under the label name "spermidine-rich wheat germ extract".
Spermidine FAQ
What is the difference between putrescine, spermidine and spermine?
They are polyamines with two, three and four amino groups. Cells make putrescine from ornithine, then add aminopropyl groups to make spermidine and then spermine, and can convert them back.
How can I tell how much spermidine is in a wheat germ extract?
Look for spermidine in milligrams per serving. The extract weight is far larger: in one trial, 750 mg of extract supplied 1.2 mg of spermidine.
Is wheat germ the only source of spermidine supplements?
No. Studies have also used a product based on Chlorella algae and soybean extract, and a purified spermidine trihydrochloride. The label should name the source.
How much spermidine does a typical diet supply?
A 2019 review estimated about 87 micromoles a day for EU adults, roughly 12.6 mg, and 54.7 micromoles for US adults, roughly 7.9 mg.
Does supplemental spermidine raise blood spermidine?
In two short studies the main change was in a related polyamine: at 15 mg a day, plasma spermine rose while plasma spermidine stayed near placebo levels, consistent with the body converting polyamines.
What is the EU limit for spermidine in supplements?
Spermidine-rich wheat germ extract may supply up to 6 mg of spermidine a day in food supplements for adults, excluding pregnant and lactating women.
How much spermidine is in Synchronicity Health capsules?
Urolithin A + Spermidine Capsules are planned with 6 mg of spermidine from a gluten-free source and 500 mg of urolithin A per 2 capsules, as a planned formula. Joining the waitlist takes no payment.
More on Spermidine
Shop and learn
Related ingredient pages
Sources
- Schwarz C, et al. Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline. Aging, 2018. DOI 10.18632/aging.101354
- Wirth M, et al. The effect of spermidine on memory performance in older adults at risk for dementia: a randomized controlled trial. Cortex, 2018. PubMed 30388439
- Schwarz C, et al. Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial. JAMA Network Open, 2022. PubMed 35616942
- Senekowitsch S, et al. High-Dose Spermidine Supplementation Does Not Increase Spermidine Levels in Blood Plasma and Saliva of Healthy Adults: A Randomized Placebo-Controlled Pharmacokinetic and Metabolomic Study. Nutrients, 2023. DOI 10.3390/nu15081852
- Keohane P, et al. Supplementation of spermidine at 40 mg/day has minimal effects on circulating polyamines: an exploratory double-blind randomized controlled trial in older men. Nutrition Research, 2024. DOI 10.1016/j.nutres.2024.09.012
- Muñoz-Esparza NC, et al. Polyamines in Food. Frontiers in Nutrition, 2019. DOI 10.3389/fnut.2019.00108
- US Food and Drug Administration. GRAS Notice Inventory, GRN 889, spermidine rich wheat germ extract. fda.gov
- UK Food Standards Agency. Register of regulated products, spermidine-rich wheat germ extract (Triticum aestivum). food.gov.uk
- US Food and Drug Administration. Questions and Answers on Dietary Supplements. fda.gov
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. If you are pregnant, nursing, under 18, in cancer care, avoiding gluten for medical reasons or taking medication, consult a qualified healthcare professional before use.