Spermidine

What it is

Spermidine is a natural polyamine [1]. The supplement used in the largest human trial was a wheat germ extract providing 0.9 mg of spermidine a day [2]. A pure spermidine product was tested at 40 mg a day [3].

How it might work

Proposed mechanism: spermidine may switch on autophagy, the cell's clean-up process [1]. In mice, dietary spermidine passed the blood-brain barrier and improved mitochondrial function in the hippocampus, the memory centre [4].

What the research says

The largest human trial, 100 adults with subjective memory decline on 0.9 mg a day for 12 months, found no change in memory test scores compared with placebo [2]. A 3-month pilot of 30 people found better memory test scores with a spermidine-rich extract, with wide uncertainty [5].

In 829 people followed for up to 20 years, higher spermidine intake from food was linked to lower death rates [6]. Large prospective human data linked higher dietary spermidine with a lower risk of cognitive impairment [4]. Food questionnaire data linked higher spermidine with lower blood pressure and less cardiovascular disease [1].

In a 13-week pilot of 40 adults over 65, 6 mg a day improved antibody responses to a third COVID-19 vaccine dose, mainly in people who had responded poorly [7]. We found no meta-analysis of spermidine trials in people.

Doses used in studies

0.9 mg a day for 12 months, wheat germ extract, 100 adults [2]. 1.2 mg a day for 3 months, 30 adults [8]. 6 mg a day for 13 weeks, 40 adults over 65 [7]. 1.5 or 3.3 mg a day for 56 days, rice germ extract, 12 adults [9]. 40 mg a day for 28 days, pure spermidine, 37 men [3]. These are study doses, not recommendations.

Safety and interactions

Common side effects: the trials reported no meaningful side effects, and adverse events were balanced between groups [2][8]. Upper limits: the highest dose tested was 40 mg a day for 28 days, so safety at higher doses is unknown [3]. Medicine interactions, pregnancy and breastfeeding: the safety data cited here do not cover them [8]. People with kidney, liver or bleeding conditions: the trials enrolled healthy adults [3]. Anyone who takes medicines or has these conditions should ask a doctor first.

Caveats and open questions

Trials disagree on memory and are small or short [2][5]. Most lifespan and disease evidence is observational [6][1]. Blood markers, such as autophagy and polyamine levels, are not health outcomes [9][3]. Several spermidine studies were run or funded by companies that sell spermidine products [2][3]. Registered trials that may add evidence are listed on this page.