Long-Term Use of Spermidine: How Safe Is It Really?
Leila WehrhahnUpdated:The essentials at a glance:
Spermidine is a polyamine that occurs naturally in the body. It is found in foods such as whole grains, mushrooms, cheese and legumes. Studies of up to 12 months using around 0.9 mg per day have reported good tolerability. Short-term intakes in the range of 15 to 40 mg have also been reported without notable issues. Within the EU, up to 6 mg per day from wheat germ extract is authorised for adults; this does not apply to pregnant or breastfeeding women. People with cancer or those taking DFMO should seek medical advice first. There is currently a lack of multi-year data on higher intakes. A balanced diet should always be the starting point.
What is spermidine and why are people interested in it?
Spermidine is a natural polyamine – a small, positively charged molecule – found in every cell of the body. It helps regulate cell growth, gene activity and, importantly, autophagy (the body’s internal “recycling” and clean‑up process).
In everyday food, spermidine is mainly found in:
- Wholegrain products (especially wheat germ)
- Mushrooms
- Matured cheeses
- Legumes (beans, lentils, chickpeas)
- Some fruits such as apples and pears
In Europe, average dietary intake is estimated at around 10–15 mg per day, though this varies considerably with diet. Food supplements can increase intake, but they do not replace a balanced, fibre‑ and polyphenol‑rich diet.
Evidence overview: Frontiers in Nutrition, 2019 – polyamines in foods and estimated intake.
Spermidine is a naturally occurring substance in the body that can trigger autophagy. It is naturally present in wholegrains, mushrooms, cheese and legumes – supplements are an additional option, not a substitute for a good diet.
What does “long-term” spermidine use actually mean?
For most supplement users, “long‑term” means taking spermidine continuously for at least 6–12 months. In clinical research, safety is assessed using:
- Reported side effects and adverse events
- Blood tests (blood count, liver and kidney function)
- Vital signs (blood pressure, heart rate)
- Neurological symptoms
- Where possible, long‑term outcomes such as cancer incidence
To date, most randomised human trials have lasted up to 12 months and used relatively low doses. This is important when thinking about safety over several years.
Spermidine Capsules
Is spermidine safe? What human studies tell us
12‑month SmartAge trial in older adults (Germany)
The longest randomised trial so far (SmartAge) followed older adults with subjective memory concerns for 12 months. Participants took either approximately 0.9 mg spermidine per day (from wheat germ extract) or placebo.
Findings:
- No clear memory benefit compared with placebo
- Very good tolerability over 12 months
- Similar rates and types of side effects in both groups
- No relevant differences in safety blood tests
- No signal of increased tumour risk
Reference: JAMA Network Open, 2022 (SmartAge study).
Earlier 3‑month pilot study
A smaller 3‑month placebo‑controlled trial (Phase IIa) suggested a possible effect on memory, but more relevant here: tolerability was again good, with no major safety concerns reported.
Reference: Cortex, 2018 (Phase IIa pilot study).
Short‑term higher‑dose data: 15–40 mg/day
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15 mg/day for 5 days: In a placebo‑controlled pharmacokinetic study, spermidine levels in the blood did not rise markedly. Instead, spermine (a related polyamine) increased, suggesting metabolic conversion. No significant safety issues were seen.
Reference: Nutrients, 2023. -
40 mg/day for up to 28 days: In a double‑blind trial in healthy men using high‑purity spermidine, standard safety blood tests remained within normal limits and no product‑related adverse effects were reported. This is short‑term only, but reassuring so far.
Reference: Nutrition Research, 2024.
Overall picture: Up to 12 months of low‑dose use appears well tolerated. Short‑term studies at higher doses (15–40 mg/day) are also unremarkable, but we do not yet have multi‑year data at those levels.
The longest RCT (12 months, ~0.9 mg/day) indicates very good tolerability. Short‑term use of 15–40 mg/day has also not raised major safety concerns. What is missing: multi‑year data with higher doses.
Does higher spermidine intake from food relate to longer life?
Observational (epidemiological) studies suggest a link between higher spermidine intake and longevity, but results are mixed and do not prove cause and effect.
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Bruneck cohort (South Tyrol, Italy): Over around 20 years, people with higher spermidine intake from food had lower overall mortality. This association remained even after adjusting for many lifestyle and health factors.
Reference: American Journal of Clinical Nutrition, 2018. -
UK Biobank: Total polyamine intake (spermidine, spermine, putrescine) showed a non‑linear relationship with mortality and cardiovascular events – moderate intakes were linked to the best outcomes. Very high intake did not necessarily mean better results.
Reference: Nutrients, 2024. -
Takayama cohort (Japan): No significant association between dietary polyamines and overall mortality was observed.
Reference: British Journal of Nutrition, 2023.
These studies look at dietary patterns, not supplements. They cannot prove that spermidine itself is responsible for any benefits, and their findings cannot be directly translated into supplement recommendations.
Higher dietary spermidine intake correlates with longer life expectancy in some, but not all, cohorts. These are observational data – they do not provide proof that supplements have the same effects.
Potential risks: cancer, kidneys and the nervous system
Spermidine interacts with cell growth and metabolism, so cancer is an obvious area of concern – but the picture is complex.
Cancer and polyamine metabolism
- Many tumours increase (upregulate) polyamine metabolism.
- DFMO (eflornithine), a drug that blocks polyamine synthesis, is being studied in cancer treatment and prevention.
- In experimental models, adding external polyamines (including spermidine) can reduce the effect of DFMO.
Practical implication: People taking DFMO or other polyamine‑lowering treatments should only consider spermidine supplements after explicit approval from their oncology team.
On the other hand:
- Some observational data suggest lower cancer mortality with higher spermidine intake from food.
- Preclinical studies describe possible anti‑tumour and immune‑modulating effects of spermidine.
At present, there is no evidence that spermidine supplements increase cancer incidence in humans. However, the data are still limited, and long‑term high‑dose trials are lacking.
Kidney and neurological safety
In the 12‑month SmartAge trial, there were:
- No signs of worsening kidney function compared with placebo
- No increase in seizure rates or major neurological events
Reference: JAMA Network Open, 2022 (SmartAge).
With active cancer treatment or DFMO use: supplements should only be taken after medical approval. Otherwise, there is currently no clear cancer‑related safety signal for spermidine – but research is ongoing.
EU and UK regulatory status: how much spermidine is allowed?
- Within the EU, the only authorised Novel Food form for supplements is “spermidine‑rich wheat germ extract (Triticum aestivum)”.
- The maximum additional intake from supplements is set at the equivalent of 6 mg spermidine per day for adults.
- Pregnant and breastfeeding women are not a target group and this must be clearly stated on the packaging.
- Specifications include strict limits for biogenic amines (e.g. cadaverine ≤ 16 µg/g) and microbiological safety criteria.
- In 2023, the Court of Justice of the European Union ruled that “spermidine‑enriched” buckwheat sprout flours are Novel Foods and need authorisation. This is a warning sign regarding non‑authorised “bio‑enriched” products sold online.
Regulatory references: EU Novel Food list and amendments; CJEU case C‑141/22.
Regulatory status checked: 12 September 2025.
Up to 6 mg/day from authorised wheat germ extract is permitted for adults. Pay attention to correct ingredient descriptions and credible specifications.
How to use spermidine safely (not medical advice)
1) Start with food: a diet‑first approach
For most health‑conscious adults, the safest and most sustainable way to increase spermidine intake is through food. This also provides fibre, minerals and polyphenols, which support overall metabolic and cardiovascular health.
Spermidine‑rich foods that are easy to include:
- Wholegrain bread, porridge oats, wheat germ
- Mushrooms (button, shiitake, oyster)
- Legumes (lentils, chickpeas, beans)
- Matured cheeses (e.g. Parmesan, Cheddar)
- Apples and pears (ideally with the skin, if appropriate)
For more background on spermidine, dietary patterns and longevity zones, see our article on spermidine, Blue Zones and food (link in original).
Table: Common spermidine‑rich foods in supermarkets
| Category | Examples | Practical tip |
|---|---|---|
| Wholegrains & germs | Wheat germ, wholemeal bread, porridge oats | Stir wheat germ into yoghurt or muesli |
| Mushrooms | Button mushrooms, shiitake, oyster mushrooms | Use 2–3× per week in stir‑fries or sauces |
| Matured cheese | Parmesan, Cheddar | Grate finely – a small amount goes a long way |
| Legumes | Lentils, chickpeas, beans | Batch‑cook and freeze to save time |
| Fruit | Apples, pears | Eat with the skin where suitable |
2) If you are considering a spermidine supplement
Product checklist for the EU/UK market
- Ingredient clearly listed as “spermidine‑rich wheat germ extract”, with reference to EU Novel Food authorisation.
- Be cautious with claims such as “spermidine‑enriched sprouts” or “bio‑enriched” if there is no Novel Food approval.
- Quality standards: ideally GMP/IFS certification, contaminant testing (heavy metals, microbiology), and identity testing.
- Clear batch numbers and origin of raw materials; people with coeliac disease should ask for a formal gluten‑free statement.
- The daily dose must be declared in mg of spermidine and should not exceed 6 mg/day.
Dosage: how much spermidine is reasonable?
- Regulatory upper limit: Do not exceed 6 mg/day from food supplements. Many products provide 1–3 mg per capsule; two 3‑mg capsules already reach the limit. 5‑mg capsules usually mean 1 capsule/day is sufficient.
- Anchored in current data: Around 0.9 mg/day showed excellent tolerability over 12 months. Higher doses (15–40 mg/day) currently only have short‑term safety data.
- Pragmatic approach: For generally healthy adults, a cautious strategy is to “start low” (for example 1–3 mg/day), then review how you feel and any side effects after several weeks.
- Timing & cycling: Take with a meal to reduce the chance of gastrointestinal discomfort. Some people choose cautious “cycling” (e.g. 8–12 weeks on, 4 weeks off) until more multi‑year data become available. This is a precaution, not a fixed rule.
Who should avoid self‑supplementation?
- People under 18 years of age.
- Pregnant or breastfeeding individuals (specifically excluded as a target group in EU authorisation).
- Anyone with active cancer, or taking polyamine‑lowering medicines such as DFMO – only supplement after approval from your oncology team.
- Those with severe, unmanaged gastrointestinal, liver or kidney disease.
- People with wheat or gluten allergy, or coeliac disease – use only products confirmed as gluten‑free.
What should you monitor if you take spermidine long term?
- Gastrointestinal symptoms (bloating, nausea, diarrhoea, abdominal discomfort).
- Headaches or other new, unexplained symptoms.
- If you have chronic conditions or take several medicines, discuss long‑term use with your GP or specialist, especially in oncology, immune‑modulating or experimental treatment settings.
You can find a curated selection of longevity‑oriented products in our longevity collection.
What do we still not know about spermidine and long-term use?
Despite growing interest, several points remain unclear:
- There are very few multi‑year (>2 years) human studies using doses close to the EU maximum (up to 6 mg/day).
- We lack large trials that track “hard” outcomes such as:
- New cancer diagnoses
- Major cardiovascular events (heart attack, stroke)
- Progression of dementia
- Absorption and metabolism are complex:
- Blood levels do not directly reflect what is happening in tissues.
- In one study, 15 mg/day mainly increased spermine, not spermidine, in the blood.
- Even 40 mg/day did not clearly change short‑term safety blood markers.
- Research is ongoing into:
- Purer and more standardised forms
- Better dose–response data
- More precise biomarkers to track effects
References: Nutrients 2023 (15 mg pharmacokinetics); Nutrition Research 2024 (40 mg study).
The science is evolving: there are reassuring short‑ to medium‑term safety data, but very few multi‑year studies at higher doses.
Alternatives and additions to spermidine for healthy ageing
If your aim is long‑term health and longevity, spermidine is only one potential piece of the puzzle. Other strategies have stronger evidence and can complement or even replace supplementation:
- Mediterranean‑style diet: High in vegetables, wholegrains, legumes, nuts and olive oil, with moderate fish and low processed meat. Strong evidence for cardiovascular and metabolic health.
- Time‑restricted eating / structured fasting: For some people, carefully planned fasting periods may support autophagy‑related pathways. This should be considered individually and may not be suitable for everyone (e.g. those with diabetes or eating disorders).
- Regular exercise: A combination of endurance (e.g. brisk walking, cycling) and strength training has robust evidence for improving cardiovascular, metabolic and musculoskeletal health.
- Food‑first approach: Combine spermidine‑rich foods with adequate protein, fibre and polyphenol‑rich plants. This supports gut health and helps maintain muscle and metabolic resilience with age.
Spermidine and cancer therapy: why DFMO matters
DFMO (eflornithine) blocks the body’s own synthesis of polyamines, including spermidine. It is being researched as a cancer treatment and for cancer prevention.
In experimental models, adding external polyamines like spermidine can interfere with DFMO’s intended effect. For this reason, anyone taking DFMO or other polyamine‑lowering regimens should not take spermidine supplements without specific approval from their oncology team.
Reference: Clinical background on DFMO in oncology and prevention.
Actionable takeaways for health‑conscious adults
- If you use a spermidine supplement: Choose an EU‑authorised wheat germ extract, keep to ≤6 mg/day, and follow the exclusion for pregnant or breastfeeding individuals. Seek medical advice if you have cancer or are on DFMO or similar treatments.
- For diet: Increase your intake of wholegrains, mushrooms, legumes, matured cheeses and apples/pears as a simple, food‑based way to support spermidine intake alongside other beneficial nutrients.
- Review regularly: Reassess your goals, tolerability and possible interactions every 3–6 months. Longevity is a long‑term project, and the foundations – diet, movement, sleep, stress and social connection – remain more important than any single supplement.
Checklist: How to evaluate spermidine products online
- Legal compliance: Ingredient listed as “spermidine‑rich wheat germ extract”; daily maximum clearly ≤6 mg/day; not promoted for pregnant or breastfeeding people.
- Manufacturing quality: GMP/IFS certification, and ideally accessible test reports for identity, microbiology and heavy metals.
- Transparency: Batch number, country of origin of raw materials, clear gluten/laboratory information.
- Clear dosage: Spermidine content per capsule (e.g. 1–3 mg) and easy comparison of price per mg.
- Customer support: Scientifically informed FAQs and responsive customer service.
Note: This article is fact‑based and aimed at health‑interested adults. It does not replace medical advice, diagnosis or treatment. Always discuss long‑term supplement use with a qualified healthcare professional, especially if you have existing conditions or take prescription medicines.